Paediatric vulvar disease

Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 1028e1041

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Paediatric vulvar disease Rosalind C. Simpson, BMBS, BMedSci, MRCP (UK), Dermatology Clinical Research Fellow a, *, Ruth Murphy, PhD, MBChB, FRCP, MMEd, BMedSci, Consultant Dermatologist b, 1 a

Centre of Evidence Based Dermatology, King's Meadow Campus, University of Nottingham, Lenton Lane, NG7 2NR, United Kingdom b Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Derby Road, Nottingham, NG7 2UH, United Kingdom

Keywords: skin disorders vulvar paediatric

Paediatric vulvar skin conditions are relatively common but often cause diagnostic difficulties for clinicians, which can lead to anxiety within the children's families. Vulvar skin conditions can be caused by various underlying aetiologies. Most are general dermatologic conditions that occur in the vulvar area, such as eczema, psoriasis, skin lesions or infections. However, other conditions such as lichen sclerosus and napkin dermatitis (‘nappy rash’) only affect the genital region. Every affected child needs a sensitive evaluation of the complaint including an assessment of the impact of the condition on the patient and her family. Paediatric vulvar disease often influences bowel and bladder habits and may lead to behavioural problems. General measures such as avoidance of irritants or soap substitution and regular use of emollients are helpful for all patients. Specific therapy depends upon the underlying diagnosis. Time spent reassuring the families, reinforcing regimens and providing written documentation can all be very helpful in successful management of paediatric vulvar skin conditions. © 2014 Elsevier Ltd. All rights reserved.

* Corresponding author. Tel.: þ44 (0) 115 8468630; Fax: þ44 (0) 115 823 1046. E-mail addresses: [email protected] (R.C. Simpson), [email protected] (R. Murphy). 1 Tel.: þ44 (0)115 9249924.

http://dx.doi.org/10.1016/j.bpobgyn.2014.07.004 1521-6934/© 2014 Elsevier Ltd. All rights reserved.

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Introduction Vulvar skin conditions are a frequent complaint in the paediatric population and vulvovaginitis is said to be one of the most common gynaecological problems in prepubertal girls [1], although it is much less common in children than in adults [2]. Such conditions are infrequently reported in the literature, leading to a reduced therapeutic evidence base. ‘Vulvitis’, ‘vaginitis’ and ‘vulvovaginitis’ are terms which are often used interchangeably to define inflammatory conditions of the lower genital tract [3]. This article focuses upon conditions of the prepubescent vulva. It should be noted that in the absence of stimulation by estrogens, the vagina is rarely the source of problems in this group of patients. Vulval skin conditions can cause considerable distress for children and their families leading to behavioural disturbances at school and home. Adding to this distress is that vulvovaginal conditions can be difficult to manage and are often poorly understood by non-specialist physicians. The cause of vulvar disease in childhood can be due to common skin conditions such as eczema or psoriasis or dermatoses that are specific to the vulvar skin, such as lichen sclerosus and nappy dermatitis. This article aims to provide a practical and when available, evidence-based approach to the aetiology, diagnosis and management of vulvar skin conditions in the prepubescent girl. Methods To identify relevant articles we searched the Medline, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) databases combining the free text terms ‘vulva*’ and ‘vulvo*’ with the medical subject heading (MeSH) terms ‘child’ and ‘skin disorder’. Databases were searched from the time of inception until 10th April 2013. No randomised controlled trials were identified and most articles were reviews, case reports or small case series. The vulva in infancy and childhood The vulva changes as children reach menarche. It is important to appreciate these changes to i) understand the normal appearance of the vulva in childhood and ii) understand the reason why certain conditions occur more frequently in children than in adults. During the first few weeks of life, the vulva and vagina are under the influence of maternal hormones that are received transplacentally [4]. In the absence of oestrogenic stimulation, the vaginal mucosa becomes thin and atrophic, and lacks protective antibodies. There are no labial fat pads or pubic hair, and the vulvar skin is thin, delicate and in close proximity to the anus. The skin is generally more vulnerable to irritants such as soaps and bubble baths. This predisposes prepubertal female genitalia to bacterial infection, especially in the presence of poor hygiene. Poor hygiene can result from habits such as ineffective hand washing, wiping from back to front following bowel movements and inadequate washing of the area. In childhood, the labia minora are relatively prominent, the hymen is thickened and the epidermal skin is thin making the vaginal introitus bright red in its normal state; these features may be mistaken as abnormalities [4]. Occasionally, labial adhesions are present, which can mimic ambiguous genitalia [4]. The pH is between neutral and alkaline which facilitates growth of normal skin bacteria rather than candida, explaining why streptococcal vulvitis is much more common than Candida infection before puberty. At puberty, the size of the labia minora and mons pubis increase due to fat deposition, pubic hair develops, the clitoris becomes more prominent and the hymenal opening increases in diameter. The pH becomes more acidic in the presence of oestrogens and the vulvar tissue can subsequently be affected by a different range of conditions that are not discussed in this article. Principles of management of vulvar skin conditions Before discussing the specific conditions seen in the vulvar area, it is important to understand initial principles of management. These apply to vulvar dermatoses affecting both adults and children.

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It is appreciated that in children and young people it might be difficult, especially in those who are very young to adhere to recommended measures. However, it is important to make the families aware of these specific recommendations and reinforce treatment plans at each visit. Extra time should be taken to address the disease process, discussing general vulvar care measures and managing expectation [5]. Information leaflets, relevant patient-oriented websites and written instructions for how to use topical agents are helpful for parents. The goal of therapy is to correct the skin's barrier function, which is usually disrupted and for in skin conditions, to reduce inflammation which usually lead to the child's symptoms. A range of environmental modifications can be undertaken to protect the skin's barrier (Box 1). Soap and other routine cleaning agents (e.g., wipes) can act as irritants and should be avoided [6]. Urinary and faecal incontinence need to be addressed as these will exacerbate, or can be the cause of the symptoms. ‘Soap substitution’, that is, using an emollient instead of soap or shower gel, with a bland cream or ointment-based emollient like petrolatum is best for cleansing. The same agent can then be used as an emollient to soothe the area and can be applied often as necessary. Inflammation reduction is achieved by topical corticosteroids. These are often ineffectively used in the vulvar area due to concerns from about side effects, particularly skin thinning. This should not be the case if used responsibly and it should be made clear to the patient and caregivers. The treatments of individual inflammatory conditions are considered in the specific sections of this article. Vulvar-specific skin conditions Lichen sclerosus Lichen sclerosus occurs almost exclusively in the genital area. Two peaks of presentation occur; these are in prepubertal girls and post-menopausal women. It is not an uncommon condition in prepubertal girls with a reported prevalence of one in 900 and this figure appears to be rising [8]. There is an increasing body of evidence to suggest that lichen sclerosus is autoimmune in nature although the exact pathogenesis remains unclear. Other autoimmune diseases are more common in adult patients with lichen sclerosus compared with controls [9] and in a case series of 70 paediatric patients, autoimmune disease occurred in 14% of patients and a family history of autoimmunity in 64% [8]. Itch and soreness are the most common presenting symptoms. These may result in dysuria and constipation. Clinical findings are typically those of well-demarcated white plaques in a figure-of-eight distribution surrounding the vulva and perianal areas. Fig. 1 demonstrates lichen sclerosus in the vulval and perineal area whilst Fig. 2 demonstrates it affecting predominantly the perianal area. Skin is usually wrinkled and may show telangiectasia that bleed to cause ecchymoses (Fig. 1). Fissuring and erosions are common. In lichen sclerosus, the vagina is not affected. Diagnosis in this age group is made

Box 1 Suggested environmental modification and vulvar care regimen for prepubertal girls with a vulvar skin complaint (modified from Fischer 2010 [7]).

Washing

Wiping External irritants Clothes

Use soap substitute with an emollient; Bathe rather than shower/supervise showering to make sure vulva is properly washed; Do not shampoo hair in the bath; Avid bubble bath. Wipe front to back; Avoid perfumed toilet paper. Avoid antifungal creams, perfumed products including wet wipes or any other cream which causes stinging. Avoid tight clothing, for example, lycra ballet clothes or leotards; Wear only cotton underwear; Change nappies regularly.

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by the typical clinical features and a diagnostic biopsy is not usually necessary since this can often be traumatic to the youngster. Given the clinical appearance, it is not uncommon for questions of sexual abuse to be raised in affected children [10]. Powell et al. found that in their case series of 70 girls, 77% of families were queried as to the possibility of sexual abuse [8]. Lichen sclerosus does have a predilection for traumatised surfaces, and clearly the presence of lichen sclerosus does not rule out sexual abuse. Features that should arouse suspicion include lichen sclerosus presenting in older prepubertal girls, poor response to treatment and coexisting sexually transmitted infections [11]. Extra genital lesions are extremely rare but present as well-demarcated atrophic plaques on the skin elsewhere. Lichen sclerosus does not usually remit at puberty, although symptoms may seem to settle. Silent progression may occur with recurrence of symptom activity at a later stage of life [12]. There is an association with the development of vulvar squamous cell carcinoma in later life and has been reported in relatively young women with lichen sclerosus since childhood [13]. Although there are no randomised controlled trials to support the use of specific therapies in this age group, case series suggest that potent or superpotent topical steroids are more effective than moderate potency preparations and do not cause side effects if used responsibly [8,14,15]. Powell suggests that once-daily application of a potent/superpotent topical steroid for 2e3 months should induce rapid alleviation of symptoms which should be followed by ‘as necessary’ applications which typically needs to be once or twice per month [8]. Topical steroids should be complemented with the regular use of an emollient, which will soothe the skin and can be used as frequently as desired (see Box 1 for additional environmental modifications that may be helpful). As with previously discussed, vulvar skin is vulnerable to steroid atrophy if overused and abused. The recommended regimen is required to induce remission of the inflammation and should not be compromised for fear of potential side effects just because the patient is a child.

Fig. 1. Vulvar lichen sclerosus. Atrophic white plaques ('porcelain-like') affecting the labia majora, periclitoral and perineal areas. Note the overall shiny nature of the skin and also an ecchymosis to the left of the perineal lesion.

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Fig. 2. Lichen sclerosus in the perineal area. Note the presence of a healed fissure centrally in the perineal area. There are also some subtle changes in the periclitoral area.

Second-line therapy with topical calcineurin inhibitors, for example, pimecrolimus 1%, has been used successfully in four girls with childhood lichen sclerosus [16] but long-term follow-up data are not available. There are theoretical concerns that topical calcineurin inhibitors could contribute towards malignant change at a later stage. In January 2006, the US Food and Drug Administration issued a boxed warning requirement based on a theoretical risk of malignancy (including lymphoma) with topical calcineurin inhibitors use. However, in the years since, analyses of epidemiologic and clinical data have failed to demonstrate a causal relationship between the use of topical calcineurin inhibitors and malignancy or lymphoma risk [17]. Napkin dermatitis Napkin dermatitis is a common inflammatory skin reaction caused by the specific environmental conditions created in the area covered by the nappy (diaper). In some countries, this is otherwise known as ‘diaper rash’. Features of this dermatitis include high humidity, maceration, friction and contact with urine and faeces [18]. The condition generally affects infants aged 9e12 months and has an estimated incidence of 7e35% [19]. The skin is affected in a characteristic distribution where the nappy is in closest contact and this includes the lower abdomen, lower lumbar region, gluteal area, genitalia and inner aspects of the thighs. ‘High-risk’ groups include those with Hirschsprung's disease or anorectal malformations. A particular unusual and potentially severe form of napkin dermatitis has been reported as a case series as re-emerging since the use of reusable nappies [20]. Children present with skin-coloured umbilicated papules or nodules with minimal erythema and can develop into an erosive dermatitis,

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known as Jacquet erosive dermatitis. This is most likely a result of reusable nappies being less absorbent than disposable ones and may be worsened by the presence of diarrhoea. However, a Cochrane systematic review in 2006 failed to find sufficient high-quality evidence to support or refute the use and type of disposable napkins for the prevention of napkin dermatitis in infants [21]. It is suggested that barrier preparations can help to prevent napkin dermatitis and there are numerous over the counter preparations marketed for this purpose. A systematic review however, found no randomised controlled trials that compared barrier preparations in the prevention of the condition [18] and so it is not possible to state which agent should is superior. A subsequent randomised controlled trial of 229 infants received petrolatum jelly, or nothing, after every nappy change, found 33% less cases of napkin dermatitis in the intervention group, although this was not statistically significant [22]. The authors do state that the intervention group had more risk factors for developing the condition though, and it is not clear whether a bigger sample size would have shown a different result. The systematic review asked a second question, which was whether one barrier preparation is better than another in treating napkin dermatitis. They found that zinc oxide impregnated into the nappy, or zinc oxide cream, and petroleum products do have some protective effect and can be used to protect the skin from irritation. Finally, a further Cochrane systematic review assessed the usefulness of topical vitamin A preparations in the treatment of napkin dermatitis, which had been postulated as a potential treatment strategy, and found no evidence to support their use in the condition [23]. On the basis of these studies, it is impossible to draw any firm conclusions about the prevention of the condition; however, experts recommend that careful cleaning of skin and regular nappy changes are imperative [22]. It remains to be proven whether barrier creams are effective on clinically normal skin to prevent the development of napkin dermatitis. Labial adhesions Labial adhesion is the term used when the labia minora fuse together in prepubescent girls. Other nomenclature used to describe the condition includes labial agglutination, labial fusion and vulvar synechiae. The incidence of labial agglutination has been reported as approximately 0.6e3.0% [24] and occurs most often in younger children up to the age of 2 years [15]. The aetiology of the condition is unknown but it is believed to be associated with the low oestrogenic state in prepubertal girls [25]. Less commonly, it occurs secondary to vulvar inflammation and irritation in which the skin becomes excoriated and denuded leading to fusion of the labial edges during the healing process [26]. Agglutination of the labia majora or minora may occur in a variable degree from the clitoris to the posterior fourchette. There is a flattened appearance to the vulva and it is not possible to see the entire vaginal opening [15]. Labial fusion is usually asymptomatic since urine can pool behind the fusion leading to maceration, secondary dermatitis, cystitis and urethritis. Management includes explaining to the parents how the fusion has arisen. Reassurance that it is a self-limiting condition and that the internal anatomy is normal is helpful for most parents. Fusion usually resolves by the age of 6 years [27]. No further treatment is necessary in an asymptomatic patient. General hygiene advice should be given as described in other parts of this article [26]. General skin conditions affecting the vulvar area Dermatitis The terms dermatitis and eczema are often used interchangeably. There are different types of dermatitis that can affect the vulvar area, in children these are predominantly atopic (i.e., patients who suffer from a tendency to eczema, asthma or hay fever) or irritant dermatitis. Atopic disease in the genital area (‘atopic vulvitis’) is part of a more widespread complaint of eczema, often combined with asthma and hay fever, or a positive family history for these complaints. Irritant dermatitis will be localised to the area where skin is in contact with the irritant. Common causes of irritant disease in children tend to relate to unintentional poor hygiene such as inadequate wiping and showering.

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Fig. 3. Atopic vulvitis. Poorly demarcated erythema in the vulvar area with mild scale and some thickening (lichenification) of the skin.

Additionally, neglecting to rinse residual soap products left on the skin (this happens less after bathing) can contribute to irritant dermatitis. Urine and faeces are common irritants so incontinence can also be a causative factor. Napkin dermatitis is a specific pattern of irritant dermatitis in the genital area and is considered separately in this article. Dermatitis is the most common cause of vulvar symptoms in prepubertal girls. In a case series of 130 girls presenting to an Australian secondary care outpatient clinic between 1996 and 1998, 33% (41/130) had atopic or irritant dermatitis [15]. A further case series study by the same authors found that 24% (9/ 38) of girls with ‘vulvovaginitis’ had clinical signs of atopic dermatitis on general skin examination [7]. A personal or family history of atopic disease is an important predictor for the development of dermatitis in children [15], especially atopic dermatitis. Fischer et al. [15] demonstrated that 85% of 41 girls with atopic or irritant dermatitis had a personal or family history of atopy. Dermatitis of any type presents as an itchy eruption which takes a relapsing-remitting course. Clinical examination shows erythematous skin that may be scaly at the peripheries (but often shiny in the flexural creases themselves) in association with leathery thickening (lichenification) and often secondary infection. Fig. 3 demonstrates features of atopic vulvitis with poorly demarcated erythema surrounding the vulvar area, minor scale and some slight thickening.

Fig. 4. Genital psoriasis. Well-demarcated, symmetrical erythema in the vulvar area and inguinocrural folds. Note the lack of typical scale and satellite lesions adjacent to the main areas of psoriasis.

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Management should begin with education about the underlying causes and subsequent environmental modification (see Box 1). Specific treatment to reduce inflammation should be with a mild or moderate potency topical corticosteroid. In a case series of nine girls with atopic dermatitis, all responded well to treatment with 1% hydrocortisone ointment, emollient and environmental changes [7]. Psoriasis When psoriasis affects the skin, it is characterised by well-defined erythematous plaques with overlying silvery scale. Symptoms include itch, irritation, pain or discomfort [28]. In flexural skin, which includes the genital area, typical scale is often not seen. There is usually a symmetrical, welldemarcated rash in the genito-inguinal region (Fig. 4) and a clue to the diagnosis is that it often exists in the perianal region and extends up into the natal cleft (Fig. 5). Satellite lesions surrounding affected genital areas may exhibit more typical psoriatic features. Classical psoriatic lesions are often present elsewhere and there may be a positive family history of psoriasis. Kapila et al. [28] reported a case series of 194 people with vulvar psoriasis, 58 of whom were children. Family history and psoriasis elsewhere on the skin were present in 47% and 78% of children, respectively, which shows that these

Fig. 5. Perianal psoriasis. Well-demarcated, symmetrical perianal erythema with scale. The lesion extends up into affect the natal cleft.

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features of history and examination are important. This is supported by Fischer et al. who found that 66% of 27 girls with vulvar psoriasis had a positive family history [29]. Other sites that should be examined if psoriasis is suspected are the scalp, nails, umbilicus and lower back as these are all classical sites. If extragenital psoriasis is mild, it is possible that the patient or parents may not know that they have the condition. Vulvar psoriasis accounts for 4% of cases of persistent vulvar symptoms [29]. In a case series of 130 prepubertal girls with a vulvar complaint, 17% were found to have psoriasis [15]. A secondary infection with Staphylococcus aureus or Group A Streptococcus has been demonstrated in a proportion of paediatric vulvar psoriasis cases which indicates there should be a low threshold for performing microbiological swab. There is no cure for psoriasis and as it is a chronic condition, emphasis should be placed on symptom control, which can partly be achieved through environmental modification (Box 1). A variety of active treatments are described in the literature for vulvar psoriasis, but many of the usual topical therapies for psoriasis, such as calcipotriol or tacrolimus, can be highly irritant in the genital area. There are no specific guidelines for treatment in children, but Kapila et al. demonstrated a good response to topical therapy with resolution of symptoms and objective return to normal skin in 92.3% of 39 children who returned for follow-up [28]. They did not however specify which topical therapies were prescribed. NICE (National Institute for Health and Clinical Excellence) guidelines for psoriasis [30] recommend short-term mild or moderate potency corticosteroids applied once or twice daily (for a maximum of 2 weeks) to sensitive sites such as the genital area. This area is vulnerable to steroid atrophy and corticosteroids should only be used for short-term treatment. It is important that families or carers are appropriately educated about this risk and advised to use large amounts of emollient to help ease symptoms. Benign growths Skin-specific benign growths are not uncommon and accounted for 12% (15/130) diagnoses in the case series by Fischer [7]. Capillary haemangiomas, also known as ‘strawberry nevi’ or ‘infantile haemangiomas’, are benign vascular tumours that appear during the first months of life and undergo rapid growth, followed by a slower period of involution. They are the most common paediatric skin tumour and affect girls more frequently than boys [31], especially those who are born prematurely or with a low birth weight [32]. The lesions usually appear within the first month of life and features may be very subtle initially, sometimes with only a faint pinkish or telangiectatic path on the skin. This then grows, becomes raised and often forms a ‘cluster’-like lesion similar to a strawberry. Ulceration is a common problem, especially during the growth phase and when sensitive sites such as the flexural vulvar area are involved. This is likely to be partly as a result of local friction. Secondary infection may occur due to ulceration. Any child with a haemangioma involving a sensitive site, causing difficulty in function (e.g., passing urine) or rapidly growing with secondary complications, should be referred to a paediatric dermatologist for specialist management. This typically includes topical or systemic steroids, or betablockers. Pigmented nevi can arise in the vulvar area in the same way that they can affect any other part of the skin. Symmetrical, regularly pigmented, non-changing lesions are clinically benign and no intervention is required. However, if there is any suspicion of malignancy as indicated by a changing lesion which increases in size or is irregular in border or colour should be referred for specialist opinion from a dermatologist. Vulvar melanoma, albeit a rare entity, has been reported in children [33]. Infections Candidal infection It should be noted that prepubertal girls rarely develop vulvovaginitis due to Candida albicans unless they have taken oral antibiotics, are diabetic or immunosuppressed [7]. It is believed that primary Candida infection only occurs in females whose genitalia are under the influence of oestrogens (i.e.,

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post-pubertal). In two retrospective studies [7,34] and one prospective study [35], which took microbiological swabs from a total of 192 girls between the ages of 2 and 12 who had symptoms of vulvovaginitis, only two were found to have C. albicans infection. These incidences occurred as a secondary complication within areas of psoriasis, rather than being caused by a primary infection. The studies did find, however, that there was a high incidence of girls being previously misdiagnosed and treated for thrush with topical preparations, where actually the vulvar symptoms were caused by specific dermatoses mainly eczema or psoriasis [7]. This indicates that non-specialists poorly understand that Candida infection in the prepubertal female is uncommon. Bacterial infection Streptococcus is the bacterium most likely to affect the genital region. It usually affects the perianal area and less commonly involves the perineum and genitalia. Studies that looked at girls with vulvovaginal symptoms (i.e., erythema, discharge and itch) aged 2e12 found that 17/80 [34] and 47/74 [35] had swabs positive for B-Haemolytic streptococcus and Streptococcus pyogenes, respectively. It seemed from these studies that a recent sore throat or upper respiratory tract infection was significant with 7/17 girls having had a recent sore throat (although duration was not stated) [34]. It should be noted that one of these studies compared their 80 cases with 11 controls [35] and the other did not use a control group, nor did they perform follow up cultures [35]. Therefore, it is not possible to say how common streptococcal positive swabs are in the general population. In their case series of 130 prepubertal females with vulvar symptoms, the underlying aetiology was found to be streptococcal vaginitis in 13 cases [15]. The classical clinical presentation of streptococcal genital infection is with perianal and/or vulvar pruritus. In a study of 23 girls with proven Group A streptococcal infection [36], symptoms in those with perianal infection ranged from perianal pruritus or tenderness to abdominal pain and rectal bleeding. In the same study, girls with vulvovaginitis complained of a variety of symptoms including dysuria, pruritus, tenderness and discharge. Perianal and/or vulvovaginal erythema was universally present on examination but not always noted by parents. Clinically, the inflammation was usually ‘beefy’ red, and occasionally associated with oedema [36]. Fissures may also be present. Before treatment is commenced for suspected genital streptococcal infection, a swab should always be taken to confirm the diagnosis. A recent randomised controlled trial compared oral penicillin against cefuroxime for Group A beta-haemolytic Streptococcus pyogenes perianal dermatitis in children 1e16 years of age [37]. Clinical improvement was more rapid in the cefuroxime group. Successful eradication of infection, as determined by a post-treatment swab, was greater in the cefuroxime group compared with the penicillin group (93% vs. 47%, p < 0.01). They therefore concluded that 7 days of cefuroxime was more efficacious than 10 days of penicillin V and should therefore be considered the treatment of choice for this condition. In cases of recurrent infection, the possibility of a foreign body or sexual abuse should be considered although these causes in practice are uncommon. Scabies Scabies, caused by the mite Sarcoptes scabiei, is most common in children and young adults and is transmitted through close physical contact. Classic clinical features in older children and adults include intense itching accompanied by the presence of characteristic skin burrows, papules, nodules, vesicles and pustules. Lesions are usually found in the finger webs and flexural regions of the wrists, elbows, axillae and perineal regions. Presentation in neonates is unlike that of adults and older children, resulting in missed or delayed diagnosis [38]. Neonates present with extensive rashes, irritability, poor feeding and failure to thrive. Genital papules and burrows are most common in males but any patient with suspected scabies should be examined in the genital area as vital clues to the diagnosis can be picked up by doing so. Permethrin cream 5% is the treatment of choice. It is safe and effective in killing both mites and eggs and is recommended by the Cochrane review group [39]. Treatment should be used by the patient and close contacts and should be applied for at least 8 h overnight from head to toe, and repeated 7 days later. Permethrin, however, is not licensed for children under 2 months of age. If in doubt, it is recommended to refer the patient to a paediatric dermatologist for specialist advice.

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Folliculitis Folliculitis describes infection and inflammation of the hair follicles that is usually caused by Staphylococcus aureus. In Fischer's case series of 130 cases of girls with vulvar disease, only four had folliculitis [7]. Secondary folliculitis may occur in conjunction with other underlying primary skin conditions or secondary to blockage of the follicles by application of greasy topical agents. The condition presents with small, evenly spaced vulvar pustules that may extend to the abdomen or buttocks. S. aureus will be cultured by a microbiological swab. Treatment involves education about how to apply topical agents appropriately, managing any underlying skin condition and the use of topical antimicrobial agents. The resolution of folliculitis is usually quick and should occur within 1e2 weeks. Genital warts It should be appreciated that genital warts, caused by human papillomavirus infection, do not necessarily indicate sexual abuse, although these lesions are uncommon in children. There is insufficient evidence to offer a reliable estimate of the frequency of sexual abuse in such cases [40]. Maternal transmission from the genital tract at delivery is a well-recognised mode, probably including those up to 2 years of age [40], whereas postnatally, transmission from adults with genital warts may occur nonsexually, for example, through sharing baths this mode of transmission is still suspect [41]. In general though, modes of transmission of genital HPV in the paediatric population are poorly described in the literature. In a large, US-based, retrospective case series of 131 prepubertal children aged between 6 months and 9 years, who were referred for evaluation of sexual abuse, a positive ruling was only made in three cases [42]. A maternal history of warts, cervical dysplasia or both was present in 66 (50%). Of 81 patients who had siblings, 40 (49.4%) had warts. Forty-five (34%) of the 131 cases had a positive maternal history for warts, dysplasia or both but also had a sibling. In that cohort, 32 (71%) of the siblings also had anogenital warts. Although sexual abuse should always be considered in such cases, examination and investigation required to rule this out can have a significant psychological impact on patients and their families. Each case needs to be assessed individually. Molluscum contagiosum Molluscum contagiosum is caused by a poxvirus and most commonly causes disease in childhood with a peak incidence between 2 and 5 years of age [43]. Lesions are seen quite commonly on the genital, perineal and surrounding skin of children, and although theoretically could be transferred through sexual abuse, this should not be considered as likely unless there are other suspicious features [40]. The virus causes individual shiny, whitish, umbilicated pearly papules that enlarge slowly and may become 5e10 mm in diameter [40]. The duration of both lesions is quite variable and although most cases are self-limiting within 6e9 months, it is not unusual for some to persist for 3 or 4 years [40]. Treatment for these lesions is not usually required and complications such as secondary infection can be prevented through avoiding scratching. A Cochrane systematic review has recently been updated and included 11 studies with 495 participants in total [44]. The review found that many common treatments for molluscum, such as physical destruction techniques (e.g., with cryotherapy or curettage), have not been adequately evaluated. Several of the treatments that were used in the included studies were not part of daily practice and there were limitations to several of these studies. Furthermore, the review was for mollusca affecting non-genital sites. The authors of the Cochrane review recommended that since most lesions will resolve within months, molluscum contagiosum can be left to heal naturally unless better evidence for the superiority of other treatment options emerge. Zinc deficiency Zinc deficiency is a rare, but important, condition to recognise. Either it is inherited in an autosomal recessive manner and presents in infancy or it occurs as an acquired condition. Inherited disease, also known as ‘acrodermatitis enteropathica’, typically starts after weaning but may be earlier if the child is not breastfed. The specific cause of zinc malabsorption is not known.

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The diagnosis is made on typical clinical features in conjunction with low serum zinc levels. The classical rash consists of striking red, erosive well-demarcated areas that may contain vesicles and pustules and affects predominantly the anogenital area, the face (perioral area) and the hands and feet. Scalp hair also thins and may be lost. There is failure to thrive, often with associated diarrhoea [45]. The condition responds quickly to dietary supplementation with zinc sulphate which should be continued lifelong. Without treatment, the prognosis is poor and can be fatal. Impact of vulvar skin disease In adults, vulvar skin diseases have a considerable impact on quality of life, social, psychosexual and psychological well-being [46,47] as they affect physical functioning and normal daily activities. In children, these conditions impact in different ways and the emotional impact can be quite severe. Symptoms of itch and soreness can be extremely distressing; one retrospective study reported 15/38 girls waking at night in distress [7] due to vulvar symptoms. Furthermore, vulvovaginal symptoms can have a subsequent effect on bowel and bladder function. Dysfunctional urination can lead to maceration and subsequent irritant dermatitis [7] whereas painful defecation can lead to chronic constipation. If an underlying vulvar skin condition has been overlooked, bladder and bowel dysfunction could be unnecessarily investigated, hence causing further distress to the patient. Symptoms may result in abnormal behaviour at school such as becoming withdrawn or disruptive and the history may be difficult to elucidate. It should not be forgotten that it is also distressing for parents or caregivers and consideration should be given to fully explaining the diagnosis, any necessary investigations and management plan, including providing written instructions and information leaflets to affected young people and their families. Sexual abuse A review article discussing paediatric vulvovaginal disease would not be complete without a mention of sexual abuse. It is understandable that the appearance of many vulvar skin conditions could raise suspicion of sexual abuse to those who are not specialists in this field. In particular, areas affected by haemangiomas or lichen sclerosus may ulcerate, bleed or cause ecchymoses, which are worrying for clinicians and parents who are unaware of the underlying diagnosis. Lichen sclerosus and other conditions such as perianal dermatitis can be mistaken for sexual abuse and occasionally abuse may trigger the inflammatory dermatosis [27]. The possibility of sexual abuse needs to be considered in any child who presents with a sexually transmitted disease [27,48], but conditions such as molluscum contagiosum and genital warts may be acquired by non-sexual means [27]. These are difficult management issues which are addressed best when there is a good rapport with the patient and her family. Summary This article has highlighted the features of common paediatric vulvar skin conditions. Not all patients with vulvar problems require access to secondary care. Many can be managed in primary care, such as molluscum and irritant dermatitis. A thorough clinical assessment of the patient patient and commencement of a vulvar care regimen should be minimum standards before referral to a specialist. Steps should be taken to minimise anxieties within families and this can be achieved through reassurance and prompt referral when indicated. Conflict of interests The authors report no conflict of interest. Funding RS works as a Clinical Research Fellow and her post is funded by a National Institute for Health Research Doctoral Research Fellowship award (DRF-2012-05-166).

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Disclaimer This article presents an independent review funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Practice points  Vulvar skin diseases in children are frequently encountered.  The impact of vulvar skin disease on the patient and her caregivers must be considered. All girls with vulvar skin disease should have a vulvar care regimen to reduce exposure to irritants and soothe the skin.  Some conditions produce clinical signs that can be mistaken for sexual abuse. This should be carefully and respectfully considered.  Primary Candida infection is extremely rare in the pre-pubertal female.

Research agenda  Randomised controlled trials are required to guide evidence-based treatment in all fields of paediatric vulvar skin disease.  Lichen sclerosus requires trial evidence to confirm whether potent or superpotent topical steroids are the best first-line therapy.  Methods of preventing napkin dermatitis should be investigated further.

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