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Intervensi untuk seborik dermatitis bayi (termasuk ruam kepala bayi)

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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 We searched for unpublished RCTs and grey literature via web search engines, and wrote to authors and pharmaceutical companies.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.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Rawatan untuk seborik dermatitis bayi (termasuk ruam kepala bayi) iaitu keadaan kulit yang mengalami keradangan dan bersisik.

Soalan ulasan

Bagaimanakah keberkesanan (dari segi mengubati dan meningkatkan kualiti hidup) dan adakah rawatan untuk seborik dermatitis bayi (ISD) yang selamat bagi kanak‐kanak sejak lahir sehingga berumur 24 bulan, apabila dibandingkan dengan yang sesama kumpulan, samada dengan tanpa rawatan atau plasebo (yang mempunyai ciri yang sama dari segi rupabentuk tetapi mengandungi bahan tidak aktif)?

Latar belakang

ISD adalah merupakan keadaan kulit yang mengalami keradangan dan boleh muncul sejurus selepas lahir, dan selalunya memakan masa berminggu ataupun bulan. Apabila ia berlaku di kulit kepala, umumnya ia dikenali sebagai ruam kepala bayi. Keadaan ini boleh melibatkan bayi dari semua etnik bangsa dan zon iklim, sehingga 71% bayi yang terlibat mengalaminya dalam tempoh tiga bulan yang pertama jangkahayat mereka.

Walaupun punca ruam kepala bayi tidak jelas, terdapat beberapa faktor yang memainkan peranan seperti pertumbuhan kulat pada kulit, minyak yang terhasil secara semulajadi pada permukaan kulit dan kehadiran hormon daripada ibu di dalam badan bayi setelah lahir. ISD selalunya adalah gejala ringan dan tidak menyebabkan kerengsaan kepada kanak‐kanak. Namun begitu, keadaan ini menyebabkan ibubapa menjadi risau.

Rawatan yang digunakan untuk kanak‐kanak yang terjejas dengan ISD adalah seperti agen pelembut, dan diikuti oleh pembuangan kulit bersisik (menggunakan syampu dan sikat rambut), serta rawatan yang digunakan bagi seborik dermatitis orang dewasa seperti antikulat dan kortikosteroid. Tidak seperti seborik dermatitis di kalangan orang dewasa, terdapat keraguan mengenai keselamatan dan keberkesanan rawatan ISD.

Ciri Kajian

Kami mengkaji 6 kajian yang kecil dengan jumlah 310 bayi, di mana 297 dirangkumkan di dalam analisis. Kajian‐kajian ini adalah jangkamasa yang pendek (10 sehingga 42 hari) dan kebanyakannya mempunyai kualiti yang rendah. Kajian‐kajian ini dilakukan di negara yang berbeza dan dinyatakan ianya dilakukan di klinik‐klinik pediatrik. Adalah dinyatakan di dalam 3 kajian bahawa 60% peserta adalah lelaki (144 lelaki di kalangan 241 bayi). Kebanyakan bayi adalah berumur di bawah tujuh bulan, namun terdapat dua kanak‐kanak berumur 7 dan 12 tahun. Darjah keterukan ISD dijelaskan sebagai ringan kepada sederhana teruk; terdapat satu kajian menyertakan 2 peserta yang mengalami ISD yang teruk.

Rawatan yang dikaji adalah: Biotin secara oral (kumpulan Vitamin B) dibandingkan dengan plasebo; krim yang mempunyai tanda dagangan atau gel dibandingkan dengan plasebo (atau kumpulan kawalan); dan losyen steroid atau salap dibandingkan dengan krim ‘licochalcone (Likuoris Cina) dan eosin (agen pewarna merah).

Empat kajian mendapat sokongan daripada syarikat farmaseutikal: di dalam 3 kajian itu, sebuah syarikat membekalkan produk intervensi; sebuah syarikat membantu analisa statistik bagi satu kajian; salah satu menggajikan seorang pengarang kajian, dan sebuah kajian mempunyai pengarang yang merupakan konsultan kepada syarikat farmaseutikal.

Bukti ini adalah terkini sehingga 22 May 2018.

Keputusan utama

Dua kajian mengkaji biotin oral berbanding plasebo. Hanya satu kajian yang mengkaji tempoh masa ruam, dan sebuah lagi kajian hanya melaporkan tiada perbezaan di antara kumpulan‐kumpulan itu. Maka, adalah tidak jelas rawatan yang mana adalah lebih berkesan.

Di dalam dua kajian yang mengkaji produk kulit yang mempunyai cap tanda dagangan berbanding plasebo, terdapat penambahbaikan bagi darjah keterukan yang sama di antara krim Promiseb (96%) dan plasebo (92%). Satu kajian mengkaji gel laktamid MEA dan syampu dibandingkan dengan hanya syampu. Penurunan kawasan permukaan yang dilitupi dengan ruam dan darjah keterukan ruam adalah lebih tinggi sedikit bagi kumpulan gel (81.4%) berbanding hanya syampu (70.2%).

Apabila membandingkan krim hidrokortisone 1% dengan losyen ‘licochalcone’ 0.025% di dalam satu kajian, kadar pemulihan, sebagai salah satu gejala keterukan, adalah hampir sama (kumpulan hidrokortisone 95.8% berbanding ‘licochalcone’ 97.1%). Penurunan kawasan permukaan badan yang terjejas adalah sama apabila dibandingkan antara salap flumetasone pivalate 0.02% (9%) dan eosin 2% solusi akuoes (7%).

Hanya dua kajian melaporkan kesan‐kesan sampingan, termasuk satu kes yang melibatkan peningkatan kemerahan kulit dengan ‘licochalcone’, manakala di dalam kajian yang membandingkan antara gel laktamid MEA dan syampu berbanding hanya syampu, tiada sebarang kesan sampingan khusus dilaporkan.

Tiada kajian yang mengukur peningkatan kualiti hidup.

Kualiti Bukti

Kualiti bukti keterangan telah diturun taraf kepada sangat rendah bagi semua hasil kajian di dalam ulasan ini kerana kebimbangan yang serius mengenai bagaimana kajian‐kajian ini dilakukan (risiko bias), bagaimana hasilnya diukur dan dilaporkan, perbezaan antara rawatan‐rawatan yang dikaji dan juga jumlah peserta yang sedikit. Maka, kami tidak dapat memastikan ketepatan mereka.

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.

Summary of findings

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Summary of findings for the main comparison. Biotin compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)

Biotin compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)

Patient or population: infantile seborrhoeic dermatitis (including cradle cap)
Setting: paediatric department in Israel (Erlichman 1981) and Australia (Keipert 1976)
Intervention: biotin
Comparison: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with biotin

Change in severity

See comment

See comment

39 (2 RCTs) randomised but only 35 included in analysis

⊕⊝⊝⊝

Very lowa

Change in severity assessed using different scales and metrics.

Erlichman 1981 reported duration of rash 1.3 (SD 0.9) months in the placebo group and 1.4 (SD 0.8) months in the biotin group, but the study did not report an explicit measure of change in severity.

Keipert 1976 did not report raw data for changes in severity but reported no statistical difference between biotin and placebo. There was "a strongly significant difference in the quantitative measure for whatever was used first" (likely due to effectiveness of the topical steroid).

Adverse events

See comment

See comment

39 (2 RCTs)

Not reported.

Quality of life

Not measured.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RCT: randomised controlled trial; SD: standard deviation.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aEvidence downgraded by three levels to very low because of serious risk of bias (incomplete outcome reporting in Erlichman 1981 and in Keipert 1976 the manufacturer analysed the data), serious imprecision (small numbers and wide confidence intervals) and serious indirectness (in Keipert 1976 study infants were also treated with topical betamethasone cream).

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Summary of findings 2. Proprietary products compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)

Proprietary products compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)

Patient or population: infantile seborrhoeic dermatitis (including cradle cap)
Setting: paediatric hospitals and practices
Intervention: proprietary products
Comparison: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with Proprietary products

Change in severity

See comment

See comment

166 randomised (2 RCTs); 160 included in analysis

⊕⊝⊝⊝

Very lowa

Change in severity assessed using different scales and metrics.

David 2013: success on IGA (day 14): 96% (95% CI 80% to 99%) with Promiseb vs 92% (95% CI 65% to 99%) with placebo; absolute risk reduction 4% (95% CI ‐13% to 32%).

Ribet 2007: lesional score reduction (reduction of surface area covered) (day 21): 81.4% with lactamide MEA gel + shampoo vs 70.2% with shampoo alone.

Adverse events

See comment

See comment

166 (2 RCTs)

⊕⊝⊝⊝

Very lowa

David 2013: no adverse events reported.

Ribet 2007: tolerance of the intervention and comparator was described as very good or good in "almost all2 in both groups, but no numerical data reported or obtainable. Specific adverse events not described but signs of discomfort similar in both groups.

Quality of life

Not measured.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; IGA: investigator global assessment; MEA gel: a moisturising agent; RCT: randomised controlled trial.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded by three levels to very low because of serious risk of bias (Ribet 2007 was an open‐label study and the study was conducted within the laboratories of the manufacturer), indirectness (different proprietary treatments used), and serious imprecision (small studies).

Open in table viewer
Summary of findings 3. Topical steroids compared to comparator for infantile seborrhoeic dermatitis (including cradle cap)

Topical steroids compared to comparator for infantile seborrhoeic dermatitis (including cradle cap)

Patient or population: infantile seborrhoeic dermatitis (including cradle cap)
Setting: paediatric departments in Thailand (Wananukul 2012) and Israel (Shohat 1987)
Intervention: topical steroids
Comparison: comparator (licochalcone 0.025% lotion; eosin 2% aqueous solution)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with comparator

Risk with topical steroids

Change in severity

See comment

See comment

105 (2 RCTs) randomised; 102 included in analysis

⊕⊝⊝⊝

Very lowa

Change in severity assessed using different scales and metrics.

Wananukul 2012: cleared by day 14: 97% (95% CI 91% to 99%) with licochalcone 0.025% lotion vs 96% (95% CI 89% to 99%) with hydrocortisone 1% lotion; absolute risk reduction 1.3% (95% CI –6% to 9%) (no difference between groups on day 14).

Shohat 1987: < 10% of body surface in both groups on day 10 (flumethasone pivalate 0.02% ointment vs eosin 2% aqueous solution)

Adverse events

See comment

See comment

105 (2 RCTs)

⊕⊝⊝⊝

Very lowa

1 participant in the licochalcone group developed an adverse effect. No other adverse events observed.

Quality of life

Not measured.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RCT: randomised controlled trial.

GRADE Working Group grades of evidence
High quality/certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality/certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality/certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality/certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded three levels to very low because of serious risk of bias (Shohat 1987 used staining agent that precludes blinding and Wananukul 2012 split‐body design has high risk of contamination), indirectness (different products used as comparator) and imprecision (small studies).

Background

Description of the condition

Infantile seborrhoeic dermatitis (ISD) is a chronic, inflammatory scaling skin condition, which typically causes redness and a patchy, greasy scaling rash in babies and young children. It occurs on hair‐bearing and intertriginous areas (where skin rubs together) where there are more numerous sebaceous glands (glands that secrete oils onto the hair follicles to lubricate the skin) (Schwartz 2006). It frequently involves the scalp, where it is commonly referred to as cradle cap, because the hard scaly patches on a red inflamed base can become thickened and confluent, resembling a cap (Elish 2006). The scalp scale can be white or yellow. ISD can also affect the eyebrows, skin behind the ears, diaper or nappy area, and skin creases of the neck and under the arms. The appearance in the skin creases may be a moist red rash rather than the yellowish scaly rash seen on the scalp (eTG Complete 2016; Janniger 1993). The rash is not itchy or painful, and usually, babies are oblivious to it, though it may cause distress to parents. It is generally self‐limiting, clearing by four to six months of age in most cases (Elish 2006; Gelmetti 2011). Diagnosis is clinical, based on the presence of the typical distribution involving the frontal and vertex areas of the scalp, the presence of yellowish adherent scale, with or without rash in the skin creases and with a (presumed) absence of itch (Gelmetti 2011).

The condition occurs worldwide and affects all ethnic groups (Palamaras 2012). It is very common, with the highest point prevalence – as reported in one large community‐based study – observed in the first three months of life (71.7%) and a high prevalence in children under one year old (44.5%), reducing to 7.5% for the age range 12 months to 23 months (Foley 2003). Most of these cases are mild. Prevalence subsequently drops to less than 1% in children aged three years old (Foley 2003). One community‐based cohort study in Germany documented the prevalence of cradle cap as at 58.4% in the first year of life (Weisse 2012). However, this study only reported doctor diagnosis of the condition, so may have under‐reported the true prevalence. One Indian study retrospectively reviewed outpatient paediatric dermatology clinic records and reported that 52.4% of children presenting under ones year of age had ISD (Sardana 2009).

Given the considerable prevalence of the condition at one year of age but low prevalence in children aged over two years, for the purposes of this review, we use the term 'infantile' loosely to refer to children aged 0 to 24 months. There is some debate about the degree to which ISD is the same entity as adult or adolescent seborrhoeic dermatitis, with some authors defining them as separate conditions bearing no relationship (eTG Complete 2016). Other authors claim that it is the same disease (Schwartz 2006), or at least similar enough to be able to extrapolate adult treatment data for the paediatric population (Cohen 2004). One study (with only 46% of participants followed up) cautiously suggested a possible link between ISD and later seborrhoeic dermatitis (Mimouni 1995), although this conflicted with the results of another smaller retrospective cohort study (Menni 1989). Much of the literature on ISD cites research in adults when discussing both causes and treatments of the condition. There is similar debate about whether ISD is part of a spectrum leading to atopic dermatitis or psoriasis, a clinical syndrome presentation for several diseases, or a separate condition (Alexopoulos 2014; Elish 2006; Gelmetti 2011; Moises‐Alfaro 2002; Neville 1975; Williams 2005). ISD has been proposed as an umbrella term encompassing several unrelated diseases, such as atopic dermatitis, psoriasis, Langerhans' cell histiocytosis, and erythroderma (reddening due to inflammatory skin disease) (Gelmetti 2011). More traditionally, ISD is seen as a separate condition, with these other disorders considered in the differential diagnosis (i.e. ISD may share signs or symptoms with these other conditions, although it is generally accepted that it can be difficult to distinguish ISD, atopic dermatitis, and psoriasis in very young infants; Gelmetti 2011; Mimouni 1995). Other differential diagnoses include intertrigo (rash in the folds of the body); contact dermatitis; and multiple carboxylase deficiency (a rare metabolic disorder causing failure to thrive and developmental delay in early infancy), including biotinidase deficiency (a specific deficiency of the enzyme that allows the vitamin biotin to be used) (Gelmetti 2011).

The cause of ISD is not well understood, but several factors are thought to play a role, involving an interplay between sebaceous gland secretions, microflora metabolism, and individual susceptibility (Ro 2005). One suggestion is that overactive sebaceous glands on the skin of newborn babies, under the influence of circulating maternal hormones, may secrete a greasy product that causes old skin cells to stay adherent to the scalp instead of falling off (New Zealand Dermatological Society 2014). It has also been suggested that the presence of increased fatty acids causes excess turnover of scalp cells leading to the flakes of ISD (Ro 2005). The bimodal occurrence of seborrhoeic dermatitis in infancy under the influence of maternal hormones then again in adolescence when androgen production increases with puberty supports a hormonal aetiology (Ro 2005; Schwartz 2006).

There is an established association between seborrhoeic dermatitis and the yeast Malassezia (formerly Pityrosporum) (Gupta 2004; Zhang 2013). The yeast degrades sebum to release fatty acids, consuming saturated fatty acids as a food source and leaving the unsaturated fatty acids (Ro 2005). Studies have identified 10 species of Malassezia that can be present on the human head, the most common being M restricta and M globosa (Ro 2005). Malassezia globosa and M restricta were identified in over 80% of people of all ages with seborrhoeic dermatitis attending an outpatient dermatology clinic (Zhang 2013). Malassezia furfur has been cultured in significantly higher frequency from children with ISD than children without ISD (Broberg 1995; Ruiz‐Maldonado 1989). The response of ISD to antifungals provides supportive evidence of the yeast playing a causative role (Taieb 1990). In one small study, Ruiz‐Maldonado cultured Malassezia from 73% of infants with seborrhoeic dermatitis and 53% of controls (Ruiz‐Maldonado 1989). This high prevalence even in controls suggests that the condition is not due simply to presence of the yeast, but that individual susceptibility plays a role. In adults, as seborrhoeic dermatitis has been noted to occur even in the presence of normal numbers of yeast, some authors argue that an altered host response to Malassezia leads to the inflammatory skin condition, rather than an overgrowth of the yeast itself (Bergbrant 1989; Gupta 2004).

Severe generalised seborrhoeic dermatitis in children can be a presentation of more serious underlying disorders. For example, desquamative erythroderma, previously known as Leiner's disease (Prigent 2002), is a rare condition involving severe ISD, which progresses to neonatal erythroderma. It can present with associated immunodeficiency, failure to thrive, and diarrhoea, and is now thought to be a cutaneous expression of numerous underlying immunodeficiency disorders, rather than a disease in itself (Gelmetti 2011). Children with human T‐cell leukaemia virus type 1 (HTLV‐1) and HIV infection have a higher incidence of seborrhoeic dermatitis (Maloney 2004).

Historically, there has been some interest in the role of essential fatty acids in ISD as the skin lesions seen in essential fatty acid deficiency states are similar in appearance to ISD. However, research findings have not supported this. Fatty acid deficiency was not present in infants with ISD in one study (Erlichman 1981). Tollesson and colleagues have described an altered pattern of serum essential fatty acids in children with ISD, which resolves in parallel with clinical resolution of the condition at any age (Tollesson 1993). This could in fact be related to Malassezia metabolism of fatty acids (Ro 2005).

Description of the intervention

While ISD is generally considered a benign and self‐limiting condition, for which no treatment may be required (Arora 2007), many treatments have been proposed and are commercially available for it. Several treatments have been studied for adult seborrhoeic dermatitis (Kastarinen 2014). These include anti‐inflammatory agents (e.g. topical steroids and calcineurin inhibitors); keratolytics (peeling agents) to soften and remove scales (e.g. salicylic acid, tar, zinc); antifungals to reduce yeast (e.g. ketoconazole, selenium sulphide); and alternative therapies, which may have multiple mechanisms of action (e.g. tea tree oil shampoo) (Schwartz 2006). Several studies of adult seborrhoeic dermatitis have noted topical steroids and topical antifungals (particularly ketoconazole) have both been effective, but they suggested that ketoconazole was better at preventing recurrences (Cohen 2004). It is unclear whether evidence for adult seborrhoeic dermatitis can indeed be applied to ISD. Treatments for adults with seborrhoeic dermatitis are the subjects of two Cochrane Reviews: a protocol 'Interventions for seborrhoeic dermatitis' (Okokon 2009) led to two systematic reviews, 'Topical antifungals for seborrhoeic dermatitis' (Okonon 2015) and 'Topical anti‐inflammatory agents for seborrhoeic dermatitis of the face or scalp' (Kastarinen 2014).

The role of treatments specifically for ISD is less clear. Topical ketoconazole (an antifungal) is safe in infants, with minimal systemic absorption detected (Brodell 1998; Taieb 1990). In rare cases, it can cause hepatotoxicity and for this reason the oral formulation (which has a higher systemic availability than topical) is not available in many countries (AMH 2018). Several authors recommend application of emollient creams or mineral or vegetable oils (e.g. olive oil, borage oil) to soften scale, with or without frequent washing with baby shampoo or medicated shampoo to lift scale, followed by brushing to mechanically remove scale (Clark 2015; Elish 2006; Gelmetti 2011; Smoker 2007). Anti‐inflammatories, such as topical hydrocortisone cream, have also been recommended for ISD, though concerns have been raised about adverse effects (Arora 2007; Wannanukul 2004). In young children, absorption in the skin is higher due to the higher skin–body ratio and therefore limiting time of use is advised (AMH 2018). Historically, the B group vitamin biotin (or also referred to as vitamin B7) has also been postulated as a treatment, because similar scalp lesions to ISD are seen as part of biotinidase‐deficiency conditions which are treated with oral biotin supplementation (Erlichman 1981; Gelmetti 2011; Keipert 1976). Additionally, complementary and alternative medicines are also used to treat ISD. Licochalcone (Chinese liquorice, extracted from Glycyrrheiza inflata and used in traditional Chinese medicine) has been studied as a treatment for ISD (Wananukul 2012).

Concerns have been raised about the use of olive oil to soften and lift scale, as it promotes a favourable environment for the yeast Malassezia furfur to proliferate and may theoretically worsen the condition (Siegfried 2012; Smoker 2007). There are also concerns about the potential for food oils applied topically to increase the risk of sensitisation and allergy as has been observed with peanut oil (Lack 2003). Young children are more susceptible to systemic adverse effects of topical corticosteroids through enhanced skin absorption (Dhar 2014). One systematic review of treatments commonly used in atopic dermatitis concluded that systemic complications can occur with (long‐term) use of topical corticosteroids (Callen 2007). Concerns have also been raised about keratolytics, such as salicylic acid, which though recommended by some (eTG Complete 2016; Smoker 2007), carry risks of systemic absorption (Morra 1996), reportedly the cause of salicylate toxicity in infants after topical application for other conditions in published case reports (Abdel‐Magid 1994; Oualha 2012). Similarly, selenium sulphide, which is used to treat other conditions (Chen 2010), has been reported to cause scalp discolouration (Fitzgerald 1997; Gilbertson 2012), and concerns have been raised about the dangers of systemic absorption (Gelmetti 2011). Additionally, some proposed treatments may have low acceptability for some cultural groups. For example, in people of African‐American or African ethnicity with tightly curled hair that requires styling after washing, frequent hair‐washing may be recommended despite indications that low hair‐washing frequency is not associated with seborrhoeic dermatitis in African‐American girls (Rucker Wright 2010).

How the intervention might work

Proposed treatments for ISD include topical antifungals aimed at reducing the yeast thought to be involved in the pathogenesis of the condition and known to be effective in treating adult seborrhoeic dermatitis. Ketoconazole belongs to a group of compounds known as azoles, which interfere with the synthesis of ergosterol, a crucial component in the fungal cell membrane that results in its breakdown (AMH 2018).

Some other treatments, such as topical steroids, have anti‐inflammatory, immunosuppressive, and antimitotic (blocking cell development, by stopping cell division) effects on fibroblasts (skin cells that produce connective tissue and facilitate wound healing) and epidermal cells (the outer layer of the skin) (AMH 2018). Other treatments rely on a mechanical effect, aiming to soften then lift away scale. These treatments include application of oils or keratolytics, followed by washing and brushing, or simply frequent washing with baby shampoos, followed by brushing. Keratolytics act by reducing the cohesion of cells in the upper layer of the skin, which causes shedding. In scaly skin conditions such as ISD, this results in removal of the scale (Schwartz 2006).

Biotin is a part of the enzymes involved in the fat and carbohydrate metabolism, influencing cell growth (including skin cells), and protein synthesis (US National Institutes of Health 2017). It is also referred to as vitamin B₇ or 'vitamin H' and can be sourced from a wide range of foods in a healthy diet (such as meat, eggs, vegetables, and fish). A scaly dermatitis is a symptom of biotin deficiency, hence its suggestion as a treatment for this condition, but the exact mechanism of action is not fully known (Erlichman 1981). Biotin is often used in skin products, but the evidence for a beneficial effect is weak.

Licochalcone is derived from liquorice root and is thought to help reduce oil production in the skin. It also has antibacterial and anti‐inflammatory properties and has been shown to reduce erythema and itching in children with atopic dermatitis (Wananukul 2012).

Why it is important to do this review

While the condition is generally self‐limiting and benign, causing no discomfort to the infant, it can cause considerable distress for parents. The myriad of commercially available and home remedies used by parents is evidence for the importance placed on ISD. Importantly, some of the currently used therapies may be harmful, as outlined above, so this review is needed to prevent harm to infants treated needlessly with those agents. Additionally, there has been no previous systematic review that we are aware of that specifically addresses seborrhoeic dermatitis in infants and children.

The plans for this review were published as a protocol 'Interventions for infantile seborrhoeic dermatitis (including cradle cap)' (Victoire 2014).

Objectives

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

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) of interventions for ISD.

Types of participants

We included children from birth to 24 months diagnosed with ISD or cradle cap, based on clinical diagnosis by a healthcare practitioner. Where a study included a small minority of participants older than 24 months, we attempted to contact the authors to obtain data for the group under 24 months of age, and if unable to obtain this, we included the study on the basis that a small number of older participants would not influence the overall results.

Types of interventions

All interventions were included, whether behavioural or pharmacological (including complementary and alternative medicines). We compared the following:

  • any treatment versus no treatment or placebo; or

  • two or more treatments or combinations of treatments.

We grouped analyses where possible into types of treatment.

Types of outcome measures

We included trials in the review even if they do not report relevant outcomes, but we did not plan to include these trials in a meta‐analysis. We would have provided reasons for exclusion from analysis had a meta‐analysis been done.

Primary outcomes

  • Change in severity score from baseline to end of study (described by measures of surface area, redness, crust, or scale) (continuous outcome).

  • Percentage of infants who developed adverse effects or intolerance to treatment (dichotomous outcome).

Secondary outcomes

  • Improvement in quality of life (QoL) as reported by parents: either continuous (score on QoL scale) or dichotomous (improved or not).

The included studies used different scales of severity or QoL, such that we were we unable to standardise these scales (so that they could be combined in a meta‐analysis), and instead describe the outcomes narratively.

Search methods for identification of studies

We aimed to identify all relevant RCTs regardless of language or publication status (published, unpublished, in press, or in progress).

Electronic searches

We searched the following databases up to 22 May 2018:

  • the Cochrane Skin Group Specialised Register using the search strategy in Appendix 1;

  • the Cochrane Central Register of Controlled Trials (CENTRAL) 2017, Issue 5, in the Cochrane Library using the strategy in Appendix 2;

  • MEDLINE via Ovid (from 1946) using the strategy in Appendix 3;

  • Embase via Ovid (from 1974) using the strategy in Appendix 4; and

  • LILACS (Latin American and Caribbean Health Science Information database, from 1982) using the strategy in Appendix 5.

Trials registers

We searched the following trials registers up to 17 June 2017:

We used the following keywords for this search: 'seborrhoeic dermatitis', 'cradle cap', 'seborrheic dermatitis'.

Searching other resources

References from included studies

We checked the bibliographies of included studies for further references to relevant trials.

Unpublished literature

We searched for unpublished RCTs and grey literature via web search engines and attempted correspondence with authors and pharmaceutical companies.

Adverse effects

We did not perform a separate search for adverse effects of interventions used for the treatment of ISD. We considered adverse effects described in included studies only.

Data collection and analysis

Some parts of the methods section of this review used text that was originally published in a Cochrane protocol on seborrhoeic dermatitis occurring in adolescents and adults (Okokon 2009). A revised protocol which formed the basis of this review was published in 2014 (Victoire 2014).

We included 'Summary of findings' tables in our review summarising the primary outcomes for all comparisons in this review.

Selection of studies

Two authors independently screened titles and abstracts to identify RCTs on ISD and assessed if the studies met the inclusion criteria, which we set out in an eligibility checklist. We retrieved the full text of these studies and references that could not be assessed based on title or abstract alone. Two authors (AV and PJM) independently carried out selection of studies for inclusion and resolved disagreement through discussion and consensus and, if necessary, further discussion with a third author (MVD). We obtained translations of studies published in languages we were unable to read. We highlighted excluded studies and stated why we excluded these studies. If we found multiple reports of the same study, we collated these so that the study, not the report, was the unit of analysis (Chandler 2013).

Data extraction and management

We adapted the Cochrane Skin Group data extraction form for our review. Two authors (PJM and AV) independently performed data extraction and made entries onto the form. A third author (MVD) resolved any disagreements. We prepared a Characteristics of included studies table that included details of participant demographics, the type of intervention and comparators, outcomes reported, and the study design.

One author (AV) checked the data and entered it into Review Manager 5 (Review Manager 2014). We used data as presented in the available publications, and attempted to contact study authors where possible to obtain further data. We compared direction and magnitude of effects reported by studies with how they appear in the review (Chandler 2013).

Assessment of risk of bias in included studies

Two authors (AV and PJM) independently entered characteristics of studies and 'risk of bias' assessments into the Characteristics of included studies table, with any disagreement resolved by consensus and, if necessary, discussion with a third author (MVD).

We assessed the risk of bias in the following domains as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011):

  • method of random sequence generation: we considered this adequate if generated centrally by means other than the immediate investigator;

  • method of allocation concealment: we considered this adequate if investigators or participants could not foresee assignment;

  • blinding of participants or carers, health professionals, or outcome assessors and whether the measurement of the outcome was likely to be affected if outcome assessors were not blinded;

  • attrition bias: loss to follow‐up and whether intention‐to‐treat analysis was used;

  • selective reporting; and

  • other bias: for example, systemic contamination or carry‐over effects with split‐lesion studies, baseline imbalance.

We assessed each item at low risk, high risk, or unclear risk of bias if insufficient information was available to adequately assess the risk and summarised the results in a 'Risk of bias' table (see Characteristics of included studies table).

Measures of treatment effect

For dichotomous outcomes, where possible we calculated absolute risk reduction with a 95% confidence interval (CI).

For continuous outcomes, we presented median severity scores and ranges for each group.

We were unable to pool studies for further analysis.

Unit of analysis issues

In the case of the single included cross‐over trial (Keipert 1976), we were unable to assess the risk of contamination due to carry over effects and we were unable to make any other assessment due to lack of reporting of results.

We analysed studies involving different interventions for different body parts on the same infant by considering each body part as the unit of analysis (Higgins 2011).

We evaluated studies involving different interventions for different parts of the same lesion for potential contamination effects.

Dealing with missing data

We attempted to contact authors of studies with missing data to obtain sufficient data for analysis and pooling, including David 2013, Ribet 2007, and Silva 1995, but were unable to obtain further data to enable the planned analyses.

If insufficient information was available to enable 'Risk of bias' assessment, we classified these studies as having high risk (if it was likely that the missing information actually referred to absence of an appropriate study process) or unclear risk (if the absence of information could have been a reporting issue). We justified how we came to our decision in the 'Risk of bias' table (see Characteristics of included studies table).

Several of our planned methodologies were not undertaken as no meta‐analysis was able to be done (refer to Differences between protocol and review section).

Assessment of heterogeneity

We assessed clinical heterogeneity of studies by examining participants, interventions, and outcomes in each study. We planned to assess statistical heterogeneity using the I² statistic and the following approximate guide to interpretation (Higgins 2011):

  • 0% to 40% might not be important;

  • 30% to 60% may represent moderate heterogeneity;

  • 50% to 90% may represent substantial heterogeneity; and

  • 75% to 100% may represent considerable heterogeneity.

We planned to take into account magnitude and direction of effects and strength of evidence for heterogeneity, but we did recognise that these thresholds can be misleading. However, studies were too heterogeneous to pool so we couldn't calculate the I² statistic.

Assessment of reporting biases

We found an insufficient number of RCTs to enable use of funnel plots to assess risk of publication bias.

Data synthesis

There was an insufficient number of studies to enable pooled analyses. Where it was not possible to perform a meta‐analysis, we summarised data from individual studies. We regarded a P value of 0.05 or less as statistically significant. We interpreted a higher P value as a finding of uncertainty, which is not the same as a lack of effect.

We used the GRADE system to assess the certainty of the evidence for each outcome (Guyatt 2011).

As none of the included studies could be pooled in a meta‐analysis, we described the results of each study individually. We grouped outcomes that measured a similar construct (such as change in severity of the lesions) and presented the results as reported in each of the relevant studies separately. We created 'Summary of findings' tables for each comparison and included all of our outcomes (summary of findings Table for the main comparison; summary of findings Table 2; summary of findings Table 3). We did not attempt to standardise outcome measures as the scales used were either too heterogeneous or there were insufficient data.

Subgroup analysis and investigation of heterogeneity

We were unable to undertake any subgroup analyses due to the low number of included studies and inability to pool them.

Sensitivity analysis

We obtained sufficient data to conduct sensitivity analyses.

Results

Description of studies

Results of the search

Electronic searches up to 22 May 2018 retrieved 179 records, 178 after removal of duplicates. There were no additional studies from searching the grey literature or the reference lists of included studies. We excluded 153 records based on titles and abstracts. We examined the remaining 25 records in full text. We excluded 18 studies in 19 reports (see Characteristics of excluded studies table). We included six studies in this review (see Characteristics of included studies table). We were unable to combine studies in a quantitative meta‐analysis. For a further description of our screening process, see the study flow diagram (Figure 1).


Study flow diagram.

Study flow diagram.

Included studies

See Characteristics of included studies table.

Study design and methods

All included studies were RCTs. One was a cross‐over design (Keipert 1976), and the other studies used a parallel‐group design. There was one split‐body parallel design study (Wananukul 2012). Due to early publication date of some of the studies, reporting on study design was inadequate for two studies (Erlichman 1981; Keipert 1976).

Study participants

Generally, studies were small ranging from 16 participants (Erlichman 1981) to 124 participants (Ribet 2007) completing the study. There were 310 participants randomised in all included studies, and 297 participants were included for analysis (4% total loss to follow‐up). Two studies did not specify the number of infants randomised, only reporting the number completing the study (Keipert 1976; Ribet 2007), so we have taken the number randomised to be the same in the absence of further information. Three studies did not report the sex of participants (Erlichman 1981; Keipert 1976; Shohat 1987). Of the remaining studies reporting the sex of the participants, 144/241 participants randomised were boys. One study included two participants outside our target age, aged seven and 12 years, out of a total of 36 participants completing the study (David 2013). We were unable to obtain unpublished data from this study with these two participants excluded, so results include those two older participants.

Two studies included 166 participants with 'cradle cap' or ISD of the scalp and did not comment on whether there was seborrhoeic dermatitis elsewhere on the body (David 2013; Ribet 2007). Four studies included 144 participants with ISD in other body sites (Erlichman 1981; Keipert 1976; Shohat 1987; Wananukul 2012).

None of the studies specified severity of the condition. David 2013 presented information on severity in a graph only (no numbers), suggesting the children had mild‐to‐moderate lesions at baseline. Similarly, Wananukul 2012 scored most children as mild to moderate (68% mild, 29% moderate, 3% severe (two participants)). Ribet 2007 reported that at baseline the minimum severity of the score was to be 12 or greater but it was unclear how this related to severity. Shohat 1987 did not describe the severity but reported that both groups were the same. Erlichman 1981 and Keipert 1976 did not report severity.

Most participants were aged under seven months (only two participants were aged over 12 months (specifically, aged seven and 12 years in David 2013)).

Setting

Most studies did not clearly describe study setting, but from the author locations, we can infer that most were probably in secondary care paediatric or dermatology clinics rather than primary care settings. Wananukul 2012 was conducted in a Thai hospital paediatric department, but it was unclear whether this was an inpatient or outpatient setting. One Israeli study took place in an day‐stay paediatric clinic (Shohat 1987). Four studies did not report the study setting (David 2013; Erlichman 1981; Keipert 1976; Ribet 2007). The studies were conducted in the USA (David 2013), France (Ribet 2007), Australia (Keipert 1976), Thailand (Wananukul 2012), and Israel (Erlichman 1981; Shohat 1987).

Interventions

Two studies compared oral biotin versus placebo (Erlichman 1981; Keipert 1976). Erlichman 1981 gave one 5 mg dose of biotin or a placebo (glucose) orally daily for two weeks. Parents were asked to stop all topical treatment during the trial. Keipert 1976 gave biotin 2 mg twice a day with the powder base as a placebo control for three weeks. Children in both groups also used topical betamethasone valerate cream diluted to 0.02%.

Two studies compared proprietary products. David 2013 compared Promiseb non‐steroidal cream twice a day for up to 14 days versus placebo cream. Both groups used second daily shampoo and brushing prior to application of the product. Ribet 2007 used a lactamide MEA gel (a moisturising agent derived from lactic acid) and shampoo daily for the first week and then shampoo two or three times a week and measure outcomes at day 42, compared to a control group that used shampoo only.

Two studies compared topical corticosteroids versus other products. Shohat 1987 used flumethasone pivalate 0.02% ointment versus eosin 2% aqueous solution for 10 days (frequency not specified). Wananukul 2012 gave all participants 1% hydrocortisone lotion for one side of the body and a licochalcone 0.025% lotion (Eucerin soothing lotion 12% base) for the other side to be applied twice a day for two weeks.

Outcome measures
Prespecified primary outcomes

Change in severity

Measures of severity were not consistent across the included studies. Three studies measured severity using a composite score of a combination of some or all of surface area, scale, crusting, and redness (Ribet 2007; Shohat 1987; Wananukul 2012). One study used a composite score (0 to 9) of clinical presentation of erythema, scales, and crusts (each scored 0 to 3) (Wananukul 2012). Shohat 1987 measured percentage body surface area affected and at baseline only, used a severity score evaluating erythema, lichenification (thickening), scabbing, or crusting, though did not report details of this severity score. Ribet 2007 assessed severity with a standardised global score measuring surface area involvement and intensity of scaling in four 'zones of the scalp', but did not report further details of how this is measured and we were unable to obtain unpublished data.

One study assessed change in severity using a global assessment score of severity, which was then dichotomised into success and failure based on the score, with a percentage success or failure reported as the primary outcome (David 2013). This study also assessed redness, crusting, scaling, and oiliness with an 'intensity score', but did not report these scores and we were unable to obtain any unpublished data (David 2013).

Keipert 1976 did not report on the components of the overall composite score of qualitative changes, but measured change in area of skin involvement alone as a percentage increase or decrease.

One study did not measure severity of the rash, but reported the age in months of the infant at disappearance of the rash, and time to resolution of the rash from commencing the intervention or placebo (Erlichman 1981).

None of the studies used a validated score of general skin disease severity or disease‐specific severity.

Adverse effects

The two older studies did not report adverse effects (Erlichman 1981; Keipert 1976).

Ribet 2007 assessed tolerance of treatment in both intervention groups, but did not describe specific adverse effects.

One study assessed adverse effects using a safety score that measured signs and symptoms of intolerance of treatment (David 2013).

One study did not describe how they assessed adverse effects but reported that there were none (Shohat 1987).

One study described a single adverse effect (Wananukul 2012).

Secondary outcomes

None of the studies reported QoL measures.

Outcomes were measured at end of treatment or until resolution.

Funding sources

Four studies had support from pharmaceutical companies: supplying the intervention product (David 2013; Erlichman 1981; Keipert 1976); assistance with statistical analysis (Keipert 1976); or study authors were employees of the pharmaceutical manufacturer (Ribet 2007), or consultants to the pharmaceutical company (David 2013). Shohat 1987 did not specify a funding source and the university funded Wananukul 2012.

Excluded studies

We assessed and excluded 18 studies (19 reports. Three studies were not RCTs (Almeyda 1974; Carboni 1982; Wannanukul 2004). Ten studies included a majority of participants outside the age range of 0 months to 24 months (Beghin 1974; Danby 1993; Dunic 2004; Goldust 2013; Harris 1972; Kozlowska 2007; Kusiba‐Charaziak 2005; Ratnavel 2007; Silva 1995; Squire 2002). Five studies included participants who did not have ISD or only few participants had the condition (Cullen 1973; Desmons 1977; Fredriksson 1972; Hall 1968; Shimelis 2012).

We excluded Wannanukul 2004 due to lack of randomisation, but we felt the study provided useful information including the observation that all lesions resolved within two weeks regardless of which treatment applied (ketoconazole 2% versus 1% hydrocortisone).

Risk of bias in included studies

Risk of bias was unclear or high for most items on each study. See the included risk of bias graphs which present our judgements about each risk of bias item presented as percentages across all included studies (Figure 2), and our risk of bias summary which details our judgements about each risk of bias item for each included study (Figure 3), with further details provided in the 'Risk of bias' table for each study under the Characteristics of included studies table.


Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.


Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

None of the included studies specified the method of random sequence generation, therefore, this was at unclear risk of bias for all included studies.

One study provided sufficient information about the allocation process to enable assessment as low risk (Wananukul 2012). The other studies did not report on allocation methods and were at unclear risk.

Blinding

Only one study was at low risk of performance bias due to adequate detailing of the procedure for identical packaging of the intervention and comparison to enable blinding of participants and personnel (Wananukul 2012). Two studies were at high risk of performance bias due to lack of blinding of participants, personnel, and outcome assessors (Ribet 2007; Shohat 1987). The two studies did not report in sufficient detail to enable assessment of risk of performance bias, and were at unclear risk (Erlichman 1981; Keipert 1976). David 2013 was at unclear risk of performance bias because the labels on overlabelled tubes of product to obscure commercial labels could possibly be removed by participants and personnel.

Shohat 1987 was at high risk of performance and detection bias due to the nature of the staining intervention (eosin) used topically making blinding impossible for participants, personnel, or outcome assessors. Ribet 2007 was at high risk of performance bias and detection bias due to being an open‐label study design.

The four other included studies were at unclear risk of detection bias due to lack of reporting of the blinding process for outcome assessment (David 2013; Erlichman 1981; Keipert 1976; Wananukul 2012).

Incomplete outcome data

For most studies, there was inadequate reporting on incomplete outcome data. However, two studies were at low risk (Shohat 1987; Wananukul 2012). Wananukul 2012 had 3/75 participants lost to follow‐up, and Shohat 1987 reported that all participants completed the study. Two studies were at high risk (David 2013; Erlichman 1981). One study had much greater loss to follow‐up in the placebo group than the treatment group (26.7% in placebo group versus 7.4% in treatment group) (David 2013). Erlichman 1981 only had one participant lost to follow‐up, but they excluded three participants from the analysis based on an outcome measure (time to resolution). The other two studies were at unclear risk of bias due to insufficient information being provided (Keipert 1976; Ribet 2007).

Selective reporting

David 2013 referred to a study protocol and reported on each study outcome referred to in the methods section of the paper. As this protocol was not published and not available to us, this was at unclear risk of bias. The other studies did not provide a separate protocol, so were at unclear risk of reporting bias.

Other potential sources of bias

We specifically assessed the risk of bias from a split‐body design in one study, with the possibility of two halves of the same scalp being treated with the two interventions (Wananukul 2012). We considered that there was a risk of cross‐contamination of the products affecting the other half of the scalp, and also a theoretical risk of systemic absorption potentially affecting the contralateral body side; therefore, confounding the effect of the comparison intervention.

We also assessed the risk of other bias based on reporting of funding sources and authors' potential conflicts of interests. Keipert 1976 was at high risk as the pharmaceutical company that manufactured the active product was involved in analysing the data. Ribet 2007 was at high risk as the study was conducted in a commercial pharmaceutical laboratory that manufactures the product being tested. David 2013 was at unclear risk as one of the authors was a consultant for Promius Pharma, the company that manufactures the studied cream and provided financial support for the study; involvement of the sponsor in study conduct and analysis was not reported. Erlichman 1981 was at unclear risk as the product (biotin) was provided by the manufacturer but involvement in study conduct and analysis was not reported. Shohat 1987 was at low risk; however, there was no information provided regarding funding of this trial or conflicts of interest of the authors. Wananukul 2012 was at high risk as they did not report funding sources or conflicts of interest.

Effects of interventions

See: Summary of findings for the main comparison Biotin compared to placebo for infantile seborrhoeic dermatitis (including cradle cap); Summary of findings 2 Proprietary products compared to placebo for infantile seborrhoeic dermatitis (including cradle cap); Summary of findings 3 Topical steroids compared to comparator for infantile seborrhoeic dermatitis (including cradle cap)

All studies reported improvement in the overall severity if not complete resolution of the rash, regardless of intervention. There was little difference in effectiveness between the intervention and comparator in all studies.

All treatments studied were well tolerated. Two studies reported either no or minimal adverse effects (Ribet 2007; Shohat 1987). Wananukul 2012 reported redness in one participant one day after treatment.

We grouped studies into the following comparisons:

  • comparison 1: biotin versus placebo;

  • comparison 2: proprietary products versus placebo;

  • comparison 3: topical steroids (anti‐inflammatory products) versus other treatments.

We were unable to pool studies for meta‐analysis due to considerable clinical heterogeneity.

We were unable to perform any subgroup analysis due to lack of data, with a small number of included studies, small study sizes, and few numerical data from these studies.

We assessed the following prespecified outcomes:

  • change in severity score from baseline to end of study (described by measures of surface area, redness, crust or scale) (continuous outcome);

  • percentage of infants who developed adverse effects or intolerance to treatment (dichotomous outcome).

No studies assessed our secondary outcome of QoL.

Comparison 1: biotin versus placebo

Two studies compared biotin to placebo (Erlichman 1981; Keipert 1976). We could not pool the studies for analysis as one study also used topical steroid (which is an active treatment) in both the intervention and placebo groups (Keipert 1976). Therefore, we described the effects of each study in this comparison separately.

1.1. Biotin versus placebo

One study compared oral biotin to placebo given daily for two weeks (Erlichman 1981).

Change in severity

Erlichman 1981 used no explicit measure of change. The only outcomes measured were age at disappearance of rash and duration of illness (from first onset and from commencement of treatment).

The duration of rash from starting biotin was 1.3 (standard deviation (SD) 0.9) months and from starting placebo was 1.4 (SD 0.8) months.

Adverse effects

Erlichman 1981 reported no adverse effects.

1.2. Biotin plus steroid versus placebo plus steroid

One study compared oral biotin to placebo but with topical steroids used by both groups in a cross‐over study (Keipert 1976).

Change in severity

Keipert 1976 measured change in severity quantitatively (percentage increase or decrease in area of skin change) and qualitatively (score out of 50), but did not report scores and percentages. Keipert 1976 reported that there was no statistical difference between biotin and placebo, but that there was "a strongly significant difference in the quantitative aspect for whatever was used first", which is probably due to the effectiveness of the topical steroid.

Adverse effects

Keipert 1976 did not report adverse effects.

GRADE assessment

Overall, the certainty of evidence for the two selected outcomes in both studies in this comparison was very low. We downgraded the evidence three levels due to serious study limitations (risk of attrition bias), serious imprecision (small studies) and serious indirectness (treated with a co‐intervention).

Comparison 2: proprietary products versus placebo

Two studies investigated the effect of proprietary products versus placebo (David 2013; Ribet 2007). These two studies could not be pooled as the treatments and comparators were different.

2.1. Promiseb versus placebo cream

Promiseb is a proprietary product described as a non‐steroidal‐containing emollient with antifungal and anti‐inflammatory properties (David 2013). The study employed a standardised shampoo and brushing regimen before applying either Promiseb or a placebo emollient cream.

Change in severity

Severity was measured at days 0, 7, and 14 using the Investigator's Global Assessment (IGA), an overall measure of severity of cradle cap (David 2013). The severity score was then dichotomised as success (score showing clear or almost clear of rash) or failure, and reported as a proportion of participants with success, rather than as a continuous outcome. IGA success was 96% (95% CI 80% to 99%) in the Promiseb group and 92% (95% CI 65% to 99%) in the placebo group at day 14, with an absolute risk reduction of 4.3% (95% CI –13% to 32%).

The study reported measuring intensity scores for scaling, crusting, erythema, and oiliness, but did not give these scores numerically, but presented them graphically with both Promiseb and placebo showing significant reduction in scores by the end of treatment (David 2013). We attempted to obtain actual scores for IGA, erythema, crusting, scaling, and oiliness from the authors, but were unsuccessful in obtaining these unpublished data. Mean percentage reduction in score of signs of cradle cap, inferred from graphical data, for the non‐steroidal cream versus placebo were: 88% versus 66% for erythema, 90% versus 58% for scaling, 78% versus 82% for crusting, and 90% versus 88% for oiliness.

Adverse effects

David 2013 reported safety scores of zero (excellent) in all participants.

2.2. Lactamide MEA gel plus shampoo versus shampoo

One study compared a regimen of cradle cap gel containing lactamide MEA and daily shampoo against daily shampoo alone (Ribet 2007).

Change in severity

The study assessed change in severity using a standardised global score of area and scale on four zones of the scalp (Ribet 2007). Decrease in lesional score was better with the cradle cap gel at every assessment, but this was reported only in terms of relative reduction in score not in absolute scores, making absolute difference in effect with the cradle cap gel difficult to assess. Day seven lesional score was reduced by 55.5% with gel plus shampoo versus 41.8% with shampoo alone (P = 0.0019), day 21 was reduced by 81.4% with gel plus shampoo versus 70.2% with shampoo alone (P = 0.0092), and day 42 improved by 95.9% with gel plus shampoo versus 86% with shampoo alone (P = 0.0144).

At the end of the study, 73.2% infants treated with gel plus shampoo had a lesional score of 0 compared with 50% in the shampoo only group (P = 0.0122).

The study also assessed erythema and signs of discomfort, which were described as being improved from baseline to the end of the study in both groups.

Adverse effects

Tolerance of the intervention and comparator was very good or good in 'almost all' in both groups, but no numerical data were reported or obtainable. Specific adverse effects were not described in this abstract.

GRADE assessment

Overall, the certainty of evidence for all outcomes in this comparison was very low. The certainty was downgraded three levels due to serious risk of bias (Ribet 2007 was an open‐label study and conducted within the laboratories of the manufacturer), indirectness (different treatments used), and imprecision (small studies).

Comparison 3: topical steroids versus other treatments

Two studies employed topical steroids as comparators, comparing them with another product (Shohat 1987; Wananukul 2012). We were unable to pool these two studies as the study designs were different. The intervention used in Shohat 1987 causes a visible stain which precludes blinding.

3.1. Hydrocortisone 1% lotion versus licochalcone 0.025% lotion

One study compared hydrocortisone against licochalcone lotion, an extract from Glycyrrheiza inflata with anti‐inflammatory and antimicrobial effects (Wananukul 2012).

Change in severity

The study assessed severity of the condition using a severity score which was "a composite score (range, 0 to 9) of the clinical presentation of erythema, scales and crusts", each of which was evaluated on a score of 0 to 3 (0 = no lesion, 1 = mild, 2 = moderate, 3 = severe), and the total categorised as mild (cumulative score 1 to 3), moderate (4 to 6), or severe (7 to 9). Severity was evaluated on days 0, 3 or 4, 6 or 7, and 14 (Wananukul 2012).

There was a 36.1% clearance of the rash in the hydrocortisone lotion group versus 44.4% clearance in the licochalcone lotion group at days three to four (P = 0.031), and no statistical difference in clearance on days six to seven or day 14. Percentage clearance by day 14 was 97% in the licochalcone lotion group (95% CI 91% to 99%) versus 96% in the hydrocortisone group (95% CI 89% to 99%), with absolute risk reduction of 1.3% (95% CI –6% to 9%).

The study did not state who did the scoring.

Median scores for severity were 0 (range 0 to 2) by day six or seven for both interventions.

In the hydrocortisone group, baseline median total severity score was 3 (range 1 and 7), reduced to 0 (range 0 to 2) at day six or seven, and 0 (range 0 to 4) at day 14. In the licochalcone group, baseline median total severity score was 3 (range 1 to 7), reduced to 0 (range 0 to 2) at day six or seven, and 0 (range 0 to 2) at day 14.

Adverse effects

One participant developed adverse effects, "a day after application, on the side that decoded as moisturiser containing 0.025% licochalcone, there was more erythema than before treatment".

Adverse effects were assessed by parent or clinician report, or both.

3.2. Flumethasone pivalate 0.02% ointment versus eosin 2% aqueous solution

One study compared the efficacy of topical flumethasone against the staining solution eosin (Shohat 1987).

Change in severity

The percentage body surface area involved changed from 39% to 30% in the corticosteroid group and from 38% to 31% in the eosin group.

At 10 days, all infants showed almost complete resolution of the skin condition, with less than 10% involvement. There was "no statistically significant difference in the rate of healing" between the two groups (Shohat 1987).

Notably, the study described that a severity score of erythema, lichenification (thickening of affected skin), scabbing, and crusting was used at baseline and was similar in the two groups, but this was not used as a measure of outcome.

Adverse effects

It was not stated how adverse effects were assessed but it was reported that there were none.

GRADE assessment

Overall, the certainty of evidence for all outcomes in this comparison was very low. The certainty was downgraded three levels due to high risk of bias (Shohat 1987 used staining agent, eosin, which precludes blinding, and Wananukul 2012 used the split‐body design, which has a high risk of contamination), indirectness (different comparators used), and imprecision (small studies).

Discussion

Summary of main results

We included six studies with 310 participants randomised. Outcomes were reported for 297 participants. Three separate comparisons were studied. None of the studies could be pooled. Some of the included studies reported two of the three outcomes required in our protocol (the primary outcomes 'Change in severity' and 'Adverse effects'). None of the studies reported QoL. The certainty of evidence for all reported outcomes was very low showing we are very uncertain about these results.

Biotin versus placebo

Two studies with 35 analysed participants compared biotin versus placebo (summary of findings Table for the main comparison).

Only one of the studies explicitly reported on change in severity, stating no significant difference between the treatment groups. The other study measured change in duration of rash, finding that the rash had a similar duration in both groups. The two studies did not report adverse effects.

Proprietary products versus placebo

Two studies with 160 analysed participants compared proprietary products versus placebo (summary of findings Table 2).

In one study, Promiseb proprietary cream and placebo were both equally effective in reducing severity. Both lactamide MEA gel plus shampoo and shampoo alone were effective in reducing severity scores (surface area covered), with a statistically significant relative decrease in the lactamide MEA gel scores.

Neither study reported adverse effects. For lactamide MEA gel and placebo, signs of discomfort were similar in both groups (and were described as being improved from baseline to the end of the study in both groups).

Topical steroids versus other treatments

Two studies with 102 analysed participants compared topical steroids versus other treatments (summary of findings Table 3).

Both hydrocortisone 1% lotion and licochalcone 0.025% lotion were similarly effective in reducing severity. Flumethasone pivalate 0.02% ointment and eosin 2% aqueous solution both reduced the affected surface area with all infants showing less than 10% involvement by 10 days. There was one reported adverse effect of erythema the day after applying licochalcone; no adverse effects were reported for hydrocortisone, flumethasone, or eosin.

Overall completeness and applicability of evidence

Despite ISD being a common presentation in primary care, we found no evidence for a number of treatments promoted in medical and lay literature (such as mineral or vegetable oils, shampoos, emollients, brushing, azoles, salicylic acid) (Elish 2006; eTG Complete 2016; New Zealand Dermatological Society 2014; Smoker 2007).

We found no studies evaluating the use of salicylic acid in ISD. The most commonly used Australian therapeutic guidelines recommend using salicylic acid to remove scale in ISD (eTG Complete 2016).

While one study referred to the use of a shampoo in both study groups (Ribet 2007), we found no studies evaluating the commonly used method of mineral or vegetable oils to soften scale followed by mechanical removal (e.g. by brushing) to manage ISD (Elish 2006; Gelmetti 2011; Smoker 2007). Therefore, the concerns of vegetable oils promoting the Malassezia yeast (Siegfried 2012; Smoker 2007), or leading to sensitisation and allergy (Lack 2003), could not be addressed by this review.

Of interest, was the absence of any study of azoles in ISD, despite many studies in adult seborrhoeic dermatitis on this intervention (Kastarinen 2014; Okonon 2015).

Most participants in the included studies were between 0 and 24 months of age. This reflects the epidemiology of the condition, which has the highest prevalence in the 0‐ to 24‐month age group. The gender of the participants was not always described, but where it was specified, it was relatively evenly split in most studies, with only one study having twice as many boys as girls (Wananukul 2012).

The studies were conducted in five different countries across multiple continents, supporting generalisability of the findings. However, the setting of the studies was either not reported or, if reported (or inferred), took place in a secondary care setting, whereas anecdotally most ISD would be managed in the community or a primary care setting. Thus, the generalisability of our review findings in this respect is uncertain.

No studies measured QoL. One of our three comparisons, biotin compared to placebo, did not measure adverse events, but the rest of the studies in this review did. One study did not describe specific adverse effects, and the other studies used unknown means of assessment. In particular, the studies did not monitor the adverse effects of steroids, such as adrenal suppression. Reporting of harm is important, also in a self‐limiting condition such as ISD, to assess if the potential benefits of the treatment weigh up to the potential for harm. Five of the six studies reported our other primary outcome 'Change in severity', using varying methods of measurement.

One Cochrane Review on adult seborrhoeic dermatitis noted a lack of research on long‐term outcomes (Kastarinen 2014). In ISD, we found no studies reporting medium‐ or long‐term follow‐up postintervention. As ISD is generally understood to be a self‐limiting skin condition, this is of less significance than for adults with seborrhoeic dermatitis. However, information about long‐term effects is important for treatments such as corticosteroids that can interfere with, for example, bone and glucose metabolism, and response to infections.

Overall, the studies identified in this review included the relevant population, that is, children under the age of two years. Studies reported effectiveness on our primary outcome of clinical severity, but not consistently on adverse events, and did not report our secondary outcome of QoL. The available trials covered only a few of the treatments commonly used in clinical practice, leaving many questions about effectiveness of these treatments unanswered.

Quality of the evidence

We were unable to pool any of the studies in each of the three comparisons in this review due to clear clinical heterogeneity (different interventions), lack of reporting of outcome data, or different study designs. Therefore, we described the results narratively. The certainty of evidence was very low for all comparisons for the two outcomes that the included studies reported (change in severity and adverse events). The evidence was downgraded due to high risk of bias (often also due to lack of blinding), indirectness (differences between studies in terms of products tested and outcomes assessed), and imprecision (generally all were small to very small studies). Studies did not use validated scores of severity, therefore all severity scores were potentially subjective in nature and we were unable to draw comparisons across the different studies. No outcomes were downgraded for inconsistency or publication bias. The older studies tended to have poorer reporting of methods and outcomes, and did not meet contemporary standards for reporting. This made assessment of risk of bias difficult, for example, when assessing concealment. It also restricted potential for comparison across studies.

One study comparing hydrocortisone 1% lotion versus licochalcone 0.025% lotion used a split‐body design (Wananukul 2012), which meant that one half of the scalp was treated with one product and the other half with the comparator. Therefore, we considered that there was a risk of cross‐contamination of the products affecting the other half of the scalp, and also a theoretical risk of systemic absorption potentially affecting the contralateral body side, therefore confounding the effect of the comparison intervention. This study was at high risk of bias.

Two studies were at high risk of other bias based on reporting of funding sources and authors' potential conflicts of interests. Keipert 1976 reported that the manufacturer of the active product was involved in analysing the data. Ribet 2007 reported that the study was conducted in a commercial pharmaceutical laboratory that manufactures the product being tested.

Potential biases in the review process

A significant limitation of this review was that we were unable to obtain further information from study authors, partly due to the often significant time elapsed since their publication.

Our judgement was to include participants up to two years of age in our inclusion criteria. While mindful of controversy about the upper age limit of ISD and whether older children may in fact have another skin condition, in fact most participants in the studies included in our review were aged below 12 months, despite varying upper age limits of inclusion criteria in those studies.

We assumed that inclusion of one study that included two children over our predefined age inclusion criteria (5% of the total study participants) would not have substantially biased the results of this review (David 2013).

Agreements and disagreements with other studies or reviews

Compared to Cochrane Reviews of adult seborrhoeic dermatitis, there was a dearth of evidence, particularly high‐quality evidence, for ISD. A wider range of interventions have been tested for adults, including, for example, calcineurin inhibitors, azole therapies, lithium, and calcipotriol (Kastarinen 2014; Okonon 2015). Unlike for adult seborrhoeic dermatitis, we were unable to draw conclusions about the best interventions for ISD due to the uncertainty of the evidence found.

One important study that was not included in this review as it was not randomised compared topical ketoconazole 2% versus topical hydrocortisone 1%, and found no statistically significant difference in effectiveness at two to three days and four to seven days, and complete resolution of lesions by two weeks in both groups, again supporting the theory that ISD will generally improve ISD regardless of treatment used (Wannanukul 2004).

The National Institute for Health and Care Excellence Clinical Knowledge Summary on seborrhoeic dermatitis recommends approaches to softening scalp ISD and gentle removal of scales, and use of a topical imidazole cream for persistent ISD. Topical corticosteroids are not advised (NICE 2013).

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Summary of findings for the main comparison. Biotin compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)

Biotin compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)

Patient or population: infantile seborrhoeic dermatitis (including cradle cap)
Setting: paediatric department in Israel (Erlichman 1981) and Australia (Keipert 1976)
Intervention: biotin
Comparison: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with biotin

Change in severity

See comment

See comment

39 (2 RCTs) randomised but only 35 included in analysis

⊕⊝⊝⊝

Very lowa

Change in severity assessed using different scales and metrics.

Erlichman 1981 reported duration of rash 1.3 (SD 0.9) months in the placebo group and 1.4 (SD 0.8) months in the biotin group, but the study did not report an explicit measure of change in severity.

Keipert 1976 did not report raw data for changes in severity but reported no statistical difference between biotin and placebo. There was "a strongly significant difference in the quantitative measure for whatever was used first" (likely due to effectiveness of the topical steroid).

Adverse events

See comment

See comment

39 (2 RCTs)

Not reported.

Quality of life

Not measured.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RCT: randomised controlled trial; SD: standard deviation.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aEvidence downgraded by three levels to very low because of serious risk of bias (incomplete outcome reporting in Erlichman 1981 and in Keipert 1976 the manufacturer analysed the data), serious imprecision (small numbers and wide confidence intervals) and serious indirectness (in Keipert 1976 study infants were also treated with topical betamethasone cream).

Figures and Tables -
Summary of findings for the main comparison. Biotin compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)
Summary of findings 2. Proprietary products compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)

Proprietary products compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)

Patient or population: infantile seborrhoeic dermatitis (including cradle cap)
Setting: paediatric hospitals and practices
Intervention: proprietary products
Comparison: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with Proprietary products

Change in severity

See comment

See comment

166 randomised (2 RCTs); 160 included in analysis

⊕⊝⊝⊝

Very lowa

Change in severity assessed using different scales and metrics.

David 2013: success on IGA (day 14): 96% (95% CI 80% to 99%) with Promiseb vs 92% (95% CI 65% to 99%) with placebo; absolute risk reduction 4% (95% CI ‐13% to 32%).

Ribet 2007: lesional score reduction (reduction of surface area covered) (day 21): 81.4% with lactamide MEA gel + shampoo vs 70.2% with shampoo alone.

Adverse events

See comment

See comment

166 (2 RCTs)

⊕⊝⊝⊝

Very lowa

David 2013: no adverse events reported.

Ribet 2007: tolerance of the intervention and comparator was described as very good or good in "almost all2 in both groups, but no numerical data reported or obtainable. Specific adverse events not described but signs of discomfort similar in both groups.

Quality of life

Not measured.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; IGA: investigator global assessment; MEA gel: a moisturising agent; RCT: randomised controlled trial.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded by three levels to very low because of serious risk of bias (Ribet 2007 was an open‐label study and the study was conducted within the laboratories of the manufacturer), indirectness (different proprietary treatments used), and serious imprecision (small studies).

Figures and Tables -
Summary of findings 2. Proprietary products compared to placebo for infantile seborrhoeic dermatitis (including cradle cap)
Summary of findings 3. Topical steroids compared to comparator for infantile seborrhoeic dermatitis (including cradle cap)

Topical steroids compared to comparator for infantile seborrhoeic dermatitis (including cradle cap)

Patient or population: infantile seborrhoeic dermatitis (including cradle cap)
Setting: paediatric departments in Thailand (Wananukul 2012) and Israel (Shohat 1987)
Intervention: topical steroids
Comparison: comparator (licochalcone 0.025% lotion; eosin 2% aqueous solution)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with comparator

Risk with topical steroids

Change in severity

See comment

See comment

105 (2 RCTs) randomised; 102 included in analysis

⊕⊝⊝⊝

Very lowa

Change in severity assessed using different scales and metrics.

Wananukul 2012: cleared by day 14: 97% (95% CI 91% to 99%) with licochalcone 0.025% lotion vs 96% (95% CI 89% to 99%) with hydrocortisone 1% lotion; absolute risk reduction 1.3% (95% CI –6% to 9%) (no difference between groups on day 14).

Shohat 1987: < 10% of body surface in both groups on day 10 (flumethasone pivalate 0.02% ointment vs eosin 2% aqueous solution)

Adverse events

See comment

See comment

105 (2 RCTs)

⊕⊝⊝⊝

Very lowa

1 participant in the licochalcone group developed an adverse effect. No other adverse events observed.

Quality of life

Not measured.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RCT: randomised controlled trial.

GRADE Working Group grades of evidence
High quality/certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality/certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality/certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality/certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded three levels to very low because of serious risk of bias (Shohat 1987 used staining agent that precludes blinding and Wananukul 2012 split‐body design has high risk of contamination), indirectness (different products used as comparator) and imprecision (small studies).

Figures and Tables -
Summary of findings 3. Topical steroids compared to comparator for infantile seborrhoeic dermatitis (including cradle cap)