Abstract

Background

Infantile seborrhoeic dermatitis (ISD) is a chronic, inflammatory, scaling skin condition, which causes redness and a greasy scaling rash in infants and young children. It can last from weeks to months, but rarely years. When it occurs on the scalp, it is referred to as 'cradle cap'. While benign and self‐limiting, irrelevant of its location on the body, it can distress parents. The effectiveness of commonly promoted treatments is unclear.

Objectives

To assess the effects of interventions for infantile seborrhoeic dermatitis in children from birth to 24 months of age.

Search methods

We searched the following databases up to 22 May 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched trials registers and checked reference lists of included studies for further references to randomised controlled trials (RCTs). We searched for unpublished RCTs and grey literature via web search engines, and wrote to authors and pharmaceutical companies.

Selection criteria

We included RCTs of interventions for ISD in children from birth up to 24 months who were clinically diagnosed by a healthcare practitioner with ISD or cradle cap. We allowed comparison of any treatment to no treatment or placebo, and the comparison of two or more treatments or a combination of treatments.

Data collection and analysis

We used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Change in severity score from baseline to end of study' and 'Percentage of infants treated who develop adverse effects or intolerance to treatment'. The secondary outcome was 'Improvement in quality of life (QoL) as reported by parents'.

Main results

We included six RCTs (one with a cross‐over design) randomising 310 children and reporting outcomes for 297 children. Most participants were aged under seven months with only two participants aged over one year (seven and 12 years old); where specified, 60% were boys. In two studies, condition severity was mild to moderate; one study included two participants with severe ISD; the other studies did not describe baseline severity or described it as body surface area affected.

The study setting was not always clear but likely a paediatric outpatient clinic in the following countries: Thailand, Israel, USA, France, and Australia.

Two studies compared oral biotin (a B group vitamin) against placebo, two studies compared proprietary products against placebo cream or a control shampoo, and two studies compared topical corticosteroids against other products. The studies were generally short‐term, between 10 and 42 days' duration; only one study followed the participants until resolution of the rash or eight months of age.

We assessed the risk of bias as unclear for most aspects due to lack of reporting, but two of the studies were at high risk of performance and detection bias due to the appearance of the intervention, the trial design (open‐label), or use of overlabelled tubes. Two trials had a high risk of attrition bias.

All the results given below were based on very low‐quality evidence. Treatment duration ranged from one week to three weeks.

For the two trials comparing biotin versus placebo (n = 35), one did not report a measure of change in severity (only change in duration of rash) while the other did not report raw data (only 'no statistically significant difference'), measured at three weeks. Neither trial reported on adverse events.

Two trials compared proprietary products against placebo (n = 160). One trial assessed change in severity via percentage success (96% of participants in non‐steroidal cream Promiseb versus 92% in placebo), and reported no adverse events (both assessed at day 14). The other trial assessed change in severity via reduction in lesional score (surface area covered), finding better results for lactamide MEA gel (a moisturising agent) plus shampoo (81.4%) compared with shampoo only (70.2%; P = 0.0092). No adverse events were described, but signs of discomfort were similar in both groups (both assessed at day 21).

In the comparison of topical steroids versus another product, change in severity was measured through evaluation of cure and body surface (n = 102).

In one trial comparing hydrocortisone 1% lotion with licochalcone 0.025% lotion, there was no significant difference in participants cured (95.8% with hydrocortisone compared to 97.1% with licochalcone). One person in the licochalcone group developed more erythema, but there were no other adverse events (both outcomes assessed at day 14). In the trial comparing flumethasone pivalate 0.02% ointment versus eosin 2% aqueous solution, a reduction in body surface area affected was seen in both groups at day 10 (9% with corticosteroid versus 7% with aqueous solution), with all infants showing less than 10% involvement. There were no adverse events (both outcomes assessed at day 10).

No studies measured QoL.

We found no trials testing commonly used treatments such as mineral oils, salicylic acid, or antifungals.

Authors' conclusions

Our review identified only a limited number of studies investigating the effects of interventions for ISD in infants and young children. Unlike the reviews investigating the effects of treatments in adults, our results showed that there is uncertainty regarding the effectiveness and safety of studied treatments due to the very low‐certainty evidence for all comparisons and outcomes.

We assessed most bias domains as at unclear risk, but there was a high risk of bias for (mainly) performance, attrition, and detection bias. Evidence was limited further by imprecision (small studies, low number of events), indirectness (mainly with the outcomes assessed), and poor trial reporting. In most studies, the prognosis for the condition was favourable regardless of intervention but interpretation is limited by the very low‐certainty evidence.

Further research is needed with large, well‐conducted, and well‐reported intervention trials, particularly of interventions commonly recommended or used, such as emollients or shampoos and brushing, antifungals, or steroids. All studies should report standardised and validated relevant outcome measures, including adverse events, severity, and QoL, and they should be conducted in primary care settings where the majority of ISD is managed. Future trials should compare against placebo, no treatment, or standard care.

Author(s)

Anousha Victoire, Parker Magin, Jessica Coughlan, Mieke L van Driel

Abstract

Plain language summary

Treatments for infantile seborrhoeic dermatitis (including cradle cap), an inflammatory, scaly skin condition

Review question

How effective (in terms of cure and improving quality of life) and safe are treatments for infantile seborrhoeic dermatitis (ISD) in children from birth up to 24 months of age, when compared with each other, no treatment, or placebo (an identical in appearance but inactive treatment)?

Background

ISD is an inflammatory scaly skin condition that can appear soon after birth, and generally lasts weeks to months. When it affects the scalp, it is commonly called 'cradle cap'. The condition affects infants of all ethnic backgrounds and climate zones, with up to 71% of infants affected within the first three months of life.

While the cause of cradle cap is unclear, factors that play a role include yeast growth on the skin, naturally occurring oils on the skin, and presence of maternal hormones in the child's body after birth. ISD is usually mild and does not cause distress to the child. However, it can concern parents.

Treatments promoted for children affected by ISD include softening agents, followed by mechanical scale removal (shampooing and combing), as well as the treatments used for adult seborrhoeic dermatitis such as antifungals and corticosteroids. Unlike seborrhoeic dermatitis in adults, there are uncertainties regarding safety and effectiveness of ISD treatments.

Study characteristics

We included six studies which were small with 310 infants, of whom 297 were included for analysis. The studies were short (10 to 42 days), and generally poor quality. Studies were in different countries, and, where stated, in paediatric clinics. Where stated in three studies, 60% were boys (144 boys among 241 infants). Most infants were aged under seven months; two were aged seven and 12 years. ISD severity where described was mild to moderate; one study included two participants with severe ISD.

The treatments tested included: oral biotin (a B group vitamin) compared to placebo; trademarked creams or gels compared to placebo (or a control group); and steroid lotion or ointment compared to licochalcone (Chinese liquorice) cream and eosin (a red staining agent).

Four studies had support from pharmaceutical companies: in three studies, a company supplied the intervention product; a company assisted with statistical analysis in one study; one employed a study author; and one had authors who were consultants to the pharmaceutical company.

The evidence is current to 22 May 2018.

Key results

Two trials assessed oral biotin versus placebo. One study only assessed duration of rash, and the other only reported that there was no differences between groups. Thus, it was unclear which treatment was more effective.

In the two trials assessing trademarked skin products versus placebo, there was similar improvement in severity between Promiseb cream (96%) and placebo (92%). One trial assessed lactamide MEA gel plus shampoo versus shampoo only. Reduction of surface area covered and severity of rash was slightly higher in the gel group (81.4%) compared with shampoo only (70.2%).

When comparing hydrocortisone 1% lotion with licochalcone 0.025% lotion in one study, cure rates, as a sign of severity, were also similar (95.8% with hydrocortisone versus 97.1% with licochalcone). Reduction in body surface area affected was similar when comparing flumethasone pivalate 0.02% ointment (9%) versus eosin 2% aqueous solution (7%).

Only two trials reported side effects, including one case of increased skin redness with licochalcone, while in the study comparing lactamide MEA gel plus shampoo versus shampoo only there were no specific side effects reported.

No studies measured improvement in quality of life.

Quality of the evidence

The quality of the evidence was downgraded to very low for all outcome measures in this review due to serious concerns with how the studies were conducted (risk of bias), how the outcomes were measured and reported, differences between the assessed treatments, and the small number of participants included. Thus, we cannot be certain of their accuracy.

Author(s)

Anousha Victoire, Parker Magin, Jessica Coughlan, Mieke L van Driel

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

The natural history of infantile seborrhoeic dermatitis, as demonstrated in the placebo groups of the included placebo‐controlled studies, is for resolution of the condition within weeks to months. As the condition is benign and likely to get better no matter what treatment is used, there is an argument for not treating the condition at all. However, parents may still seek active intervention. It is important that any such intervention is effective, but especially that any intervention is safe. Overall, the certainty of evidence for treatments for included studies was very low, so we are unable to make conclusions regarding the treatment comparisons assessed in this review (i.e. oral biotin, Promiseb, lactamide MEA gel plus shampoo, licochalcone 0.025% lotion, hydrocortisone 1% lotion, flumethasone pivalate 0.02% ointment, and eosin 2% aqueous solution).

Implications for research 

More research is needed into the effectiveness of interventions for infantile seborrhoeic dermatitis.

Interventions to be studied should include commonly used or guideline‐recommended treatments such as mineral or vegetable oils, emollients, shampooing and brushing to remove scale, antifungal agents (e.g. azoles), steroids, or salicylic acid topical treatments (we note there are published case reports of salicylate toxicity in infants after topical use (Abdel‐Magid 1994; Oualha 2012), highlighting the need for further studies evaluating the effectiveness and safety of this treatment) (Arora 2007; Clark 2015; Elish 2006; eTG Complete 2016; Gelmetti 2011; New Zealand Dermatological Society 2014; NICE 2013; Smoker 2007). These should be compared against no treatment, placebo, or standard care as the comparator.

Future studies should provide a clearer description of the study participants, especially information about coexistence or development of other skin conditions such as atopic dermatitis.

Further studies should use standardised dosing regimens to enable cross‐study comparisons and have clearly defined, relevant, and validated outcomes, including severity scores and QoL scores (including parental QoL). They should also measure and report in detail adverse effects and short‐ and long‐term safety. Particularly, questions regarding salicylate toxicity with use of salicylic acid, and olive oil potentially facilitating growth of Malassezia need to be answered with studies designed to assess adverse effects as well as efficacy. Given that the condition is common with anecdotally reported widespread use of proprietary non‐prescription treatments by parents, inclusion of economic analyses in future trials would also be of value. Standardised outcome measures will facilitate future meta‐analysis; for example, a validated standardised score for severity would facilitate comparison between studies.

Studies should involve sample sizes determined by appropriate power calculations to be adequate to detect meaningful difference in outcomes. They should, where practical, be double blinded to reduce performance and detection bias, and be funded independently. Randomisation using the participant as the unit of randomisation rather than split‐body or split‐lesion designs is needed especially in evaluation of adverse effects and quality of life. It is also essential that research is conducted in primary care settings so that findings are generalisable to the setting in which most infantile seborrhoeic dermatitis is managed.

The reporting of future research should enable clinicians to fully evaluate them and be confident of their findings by following the CONSORT guideline providing recommendations for clinical trials (Schulz 2010). Future studies should provide sufficient information about study design to enable assessment and pooling. This should include publication of protocols in a trials registration database, reporting of methods of allocation concealment, and reporting of results numerically as well as graphically.

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