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).