CED

Clinical dermatology • Concise report

Clinical and Experimental Dermatology

Treatment of vulvar lichen sclerosus with topical corticosteroids in children: a study of 72 children G. A. Casey, S. M. Cooper and J. J. Powell Dermatology Department, Oxford University Hospitals NHS Trust, Oxford, UK doi:10.1111/ced.12519

Summary

Treatment of vulvar lichen sclerosus (VLS) in children by topical corticosteroids gives control of symptoms and some resolution of physical signs, but large studies are limited. We report the largest study of 72 prepubertal girls with VLS, 62 of whom were prospectively treated with daily application of an ultrapotent topical corticosteroid (UPTC), clobetasol propionate 0.05% ointment, for 3 months, with a follow-up period of 4–8 years [the remaining 10 patients responded to mild to moderate potency topical corticosteroids (MPTCs)]. The results were compared with a retrospective study of 31 prepubertal girls with VLS treated with MPTCs. MPTCs led to symptom clearance in 32.2% of patients, whereas UPTC led to symptom clearance in 72.6% of patients. Improvement in clinical signs following UPTC occurred in 90.3% of children at 3 months, with total resolution of clinical signs occurring in 29.2% at the 4-year follow-up or at puberty. No serious adverse effects occurred with UPTC treatment. In children with VLS, UPTCs relieve symptoms, resolve signs and possibly prevent scarring. UPTCs should therefore be the treatment of choice for VLS in children.

Lichen sclerosus (LS) is an inflammatory skin disorder with a predilection for the anogenital area. Recent guidelines from the British Association of Dermatologists advocate the use of ultrapotent topical corticosteroids (UPTCs) for treatment of genital LS of all age groups, with specific guidance given on initial and maintenance treatment for adults.1 Reports on the use of potent topical corticosteroids and UPTCs in children with VLS are limited to small studies.2–6 We have previously reported the use of UPTCs in two studies of 317 and 548 girls, although specific treatment outcomes were not examined. The aim of this study was to determine the optimum treatment for a large cohort of prepubertal girls with VLS with regard to potency, efficacy and safety of topical corticosteroids. Correspondence: Dr Genevieve Casey, Department of Dermatology, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 13 June 2014

ª 2014 British Association of Dermatologists

Report Ethics approval was obtained from the hospital’s ethics committee, and informed consent was obtained from the parents for investigation and treatment of the children in the study. Over a 10-year period, we identified 72 children with VLS in the paediatric vulvar clinic of Oxford University Hospitals NHS Trust. VLS was diagnosed by clinical appearance in girls who were pre-menarche and aged ≤ 14 years. A cohort of 31 patients treated with mild to moderate potency topical corticosteroids (MPTCs; hydrocortisone 1% or clobetasol butyrate 0.05% ointment) were studied retrospectively. Twentyone patients from this cohort and 41 patients newly referred to the paediatric vulvar clinic and diagnosed with VLS made up the cohort of 62 patients who were studied prospectively. The remaining 10 patients responded well to MPTCs, and so were not studied further. Treatment was initiated with clobetasol propionate 0.05% ointment, which was applied daily for 3 months, and then as necessary for maintenance

Clinical and Experimental Dermatology (2015) 40, pp289–292

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treatment to control symptoms. One adult fingertip unit was applied to the vulvar and perianal areas at each application, and 30 g tubes were supplied for the 3-month treatment course. Patient demographics are shown in Table 1. Data from the prospective analysis of 62 patients were collected at diagnosis and initiation of treatment, at follow-ups at 3, 6 and 12 months, and then annually for 4–8 years or until puberty if this occurred earlier than 4 years (Table 2). Response to treatment was graded according to response of symptoms and signs (Table 3). Response of symptoms to UPTC treatment at the 3month follow-up showed that 96.8% of children had marked improvement of symptoms, with 72.6% being completely clear of symptoms. At the 4-year follow-up or puberty, 60.4% remained symptom-free and required no treatment, while 37.5% were much improved but had occasional symptoms, requiring ‘maintenance treatment’ typically less than weekly, and in some as rarely as six times a year. Only one patient (2.1%) had symptoms needing treatment up to twice weekly. Three further patients (4.8%) in the prospective cohort who had clinical signs of VLS were asymptomatic at diagnosis. The retrospective analysis of 31 patients treated with MPTCs revealed improvement in all patients, but 67.7% reported the need to apply MPTCs more often than twice weekly (and often daily) on a long-term basis to control symptoms. A 3-month course of UPTC resolved symptoms more effectively than MPTCs, with a higher percentage of children achieving complete clearance of symptoms and thus a break from treatment. We found that this regimen seemed to ‘switch off’ symptoms rapidly and effectively, even in patients who had required almost continual treatment with MPTCs, sometimes for many years. The few patients requiring maintenance UPTC following treatment (24.2%) needed less frequent application than with MPTCs, typically twice monthly rather than daily as for MPTCs. Therefore, the total dose of corticosteroid used is less if UPTCs are used at the onset, because the maintenance treatment required after the first 3 months is much reduced. Symptom response to UPTCs in prepubertal girls with VLS has been previously reported in much smaller cohorts, with shorter treatment duration or shorter length of follow-up than our study.3–5,7–9 Our finding that UPTCs are effective in relieving symptoms of VLS correlates with these studies. The higher recurrence of symptoms in smaller studies compared with ours may be due to the shorter duration of their initial treatment

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Table 1 Patient demographics. Mean (range) Age of patients, years At presentation At onset of symptoms Duration of symptoms before diagnosis, years

6.7 (3–14) 5.2 (1–12) 1.5 (0.4–5 )

Table 2 Results of treatment of vulvar lichen sclerosus with ultrapotent topical corticosteroid (clobetasol propionate 0.05% ointment) in 62 children.

Symptom response, n (%) Clear Moderate Poor Negative Resolution of signs, n (%) Total Partial Nil Negative Treatment frequency, n (%) Daily Twice weekly or more Less than weekly Nil Surgery required

After 3 months of treatment (n = 62)

After 1 year of treatment (n = 60)

At 4 years or puberty (n = 48)

45 15 2 0

(72.6) (24.2) (3.2) (0)

33 26 1 0

(55.0) (43.3) (1.6) (0)

29 18 1 0

(60.4) (37.5) (2.1) (0)

14 42 6 0

(22.6) (67.7) (9.7) (0)

15 42 3 0

(25.0) (70.0) (5.0) (0)

14 34 0 0

(29.2) (70.8) (0) (0)

62 (100) 0 0 0 2* (3.2)

0 3 24 33 0

(0) (5.0) (40.0) (55.0) (0)

0 1 18 29 0

(0) (2.1) (37.5) (60.4) (0)

*Labial division. Table 3 Grading of symptom response and resolution of signs after treatment. Definition Symptom response Clear Symptom-free during the treatment Moderate Symptom improvement and/or partial resolution of individual symptoms Poor No change in symptoms Negative Worsening of symptoms Resolution of signs Total Complete resolution of all signs including pallor and atrophy (apart from scarring) Partial Complete resolution of purpura, hyperkeratosis, fissures, erosions, but persistence of pallor or textural changes Nil No change in signs Negative Worsening of signs

Symptoms: anogenital pruritus, soreness, pain, urinary problems, perianal symptoms, constipation, bleeding. Signs: Erythema, pallor, atrophy, hyperkeratosis, purpura, telangiectasia, fissures, scarring (fusion or loss of labia), erosions, bullae, absence of signs and return to normal.

ª 2014 British Association of Dermatologists

Treatment of vulvar LS in children  G. A. Casey et al.

course, as our cohort, who were treated for 3 months, reported fewer relapses. Response of the vulvar signs to 3 months of treatment with UPTCs was good overall. Clinical improvement occurred in 90.3% of patients after 3 months, and total resolution of signs (apart from scarring), including return to normal colour and texture, occurred in 22.6% of patients. Two children underwent surgery for complete labial fusion that had caused urinary, menstrual and/or potential sexual difficulties. After 4 years of follow-up or at puberty, total resolution of signs (apart from scarring) occurred in 29.2% of children to the extent that it was impossible to make a clinical diagnosis of VLS in these children. Of those with remaining signs of VLS, these were very minor in many cases, with pallor and loss of labia minora. Fusion of the labia minora was mostly reversible with UPTC treatment, and major scarring, burying of the clitoris and introital stenosis were not seen. Five of the children had substantially longer symptom duration before treatment compared with the rest of the cohort, and these patients were part of the group whose signs did not resolve fully on treatment. This adds to the indirect evidence that UPTCs may prevent scarring if used early in the course of the disease. Some studies with potent and ultrapotent topical corticosteroids have shown a high percentage of girls with complete resolution of signs after treatment.2,5 Smith and Fischer9 showed similar results to our study, with almost three-quarters of girls retaining some signs of VLS when entering puberty. Treatment with UPTC was associated with very few side effects. Difficulty with application of the ointment formulation was reported by 11.3%, but this was noted and cream formulation, so did not affect clearance rates. Development of telangiectasia and reversible erythema were observed in 19.4% and 12.9%, respectively (Table 4). We noted an occasional early increase in hair growth at the application site; this

Table 4 Side effects of 3 months of treatment with ultrapotent topical corticosteroid (clobetasol propionate 0.05% ointment).

Side effects Difficulty of application of ointment formulation, with preference for cream formulation Telangiectasia at application site Erythema at application site*

*Reversed on cessation of treatment.

ª 2014 British Association of Dermatologists

Patients (n = 62), n (%) 7 (11.3) 12 (19.4) 8 (12.9)

reduced as the dose reduced, but was not formally recorded. Treatment failure, as defined by poor symptom response, no resolution of signs, or requirement for a maintenance treatment frequency of ≥ 2 times/ week, was encountered in ≤ 5% of girls, and was usually due to undertreatment. This was because parents were anxious about UPTC use, or allowed the child to supervise their own treatment, or because symptoms resolved so rapidly on initiation of treatment that the 3-month treatment course was not completed. With regard to secondary labial fusion, the majority of patients responded to UPTC with gradual separation of the labia; however, fusion recurred in some when the treatment was stopped, but it also resolved spontaneously. Surgery becomes necessary only if the fusion is leading to urinary difficulties, or in older teenagers, if sexual intercourse is difficult. In such cases, it is important that dilators are used postoperatively to maintain the separation of the labia. In patients with asymptomatic VLS, we advise a 3-month course of UPTC treatment. The aim of this is to prevent the development of symptoms and resolve the physical signs, possibly reducing the risk of scarring and preventing persistence of the disease into adult life, when there is a risk of scarring, dyspareunia and development of squamous cell carcinoma. In conclusion, we report the largest prospective cohort study so far reported of 62 prepubertal girls with VLS treated with daily application of UPTC for 3 months and then as required for symptom maintenance thereafter. UPTC treatment was more effective than MPTCs, with a higher percentage of patients achieving complete clearance of symptoms. The majority of patients treated with the 3-month UPTC course either did not require further maintenance treatment for symptoms, or required maintenance treatment for symptom flares less than weekly. Improvement in clinical signs occurred in all patients with UPTC, although evidence of some residual signs remained in almost three-quarters of patients at the 4-year follow-up or at puberty. UPTC was also effective at separating labial fusion secondary to VLS. The treatment was attended with few side effects both in the short and long term. We recommend that for VLS in prepubertal girls, even if asymptomatic, a 3-month course of UPTC is the treatment of choice. This is more aggressive than the guidelines for adult women but seems to offer a chance of complete symptomatic and clinical resolution.

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References Learning points ● We carried out a prospective study of 62 pre-

pubertal girls with VLS treated with UPTC (clobetasol propionate 0.05% ointment), and compared the results with a retrospective study of 31 girls treated with MPTCs. ● UPTC applied daily for 3 months was effective in clearing symptoms in 72.6% of children, whereas MPTCs cleared symptoms in only 32.3% of children. ● UPTC applied daily for 3 months resulted in improvement of clinical signs in all children, with some clinical evidence of VLS remaining in 70.8% of girls at 4 years follow-up or puberty. ● After the initial 3-month treatment with UPTC, 95% of girls did not require any further treatment, or required treatment less than once weekly. ● The side effects of 3 months of treatment with clobetasol propionate 0.05% ointment were minimal, with < 20% of girls experiencing side-effects, which included difficulty in applying the ointment formula, and development of telangiectasia or erythema. ● For VLS in prepubertal girls, UPTC applied daily for 3 months is the treatment of choice.

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1 Neill SM, Lewis FM, Tatnall FM, Cox NH. British Association of Dermatologists’ guidelines for the management of lichen sclerosus 2010. Br J Dermatol 2010; 163: 672–82. 2 Fischer G, Rogers M. Treatment of childhood vulvar lichen sclerosus with potent topical corticosteroid. Pediatr Dermatol 1997; 14: 235–8. 3 Garzon MC, Paller AS. Ultrapotent topical corticosteroid treatment of childhood genital lichen sclerosus. Arch Dermatol 1999; 135: 525–8. 4 Smith YR, Quint EH. Clobetasol propionate in the treatment of premenarchal vulvar lichen sclerosus. Obstet Gynecol 2001; 98: 588–91. 5 Patrizi A, Gurioli C, Medri M, Neri I. Childhood lichen sclerosus: a long-term follow-up. Pediatr Dermatol 2010; 27: 101–3. 6 Focseneanu MA, Gupta M, Squires KC et al. The course of lichen sclerosus diagnosed prior to puberty. J Pediatr Adolesc Gynecol 2013; 26: 153–5. 7 Cooper SM, Gao XH, Powell JJ, Wojnarowska F. Does treatment of vulvar lichen sclerosus influence its prognosis? Arch Dermatol 2004; 140: 702–6. 8 Powell J, Wojnarowska F. Childhood vulvar lichen sclerosus: an increasingly common problem. J Am Acad Dermatol 2001; 44: 803–6. 9 Smith SD, Fischer G. Childhood onset vulvar lichen sclerosus does not resolve at puberty: a prospective case series. Pediatr Dermatol 2009; 26: 725–9.

ª 2014 British Association of Dermatologists

Treatment of vulvar lichen sclerosus with topical corticosteroids in children: a study of 72 children.

Treatment of vulvar lichen sclerosus (VLS) in children by topical corticosteroids gives control of symptoms and some resolution of physical signs, but...
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