Ultrapotent Topical Corticosteroid Treatment of Childhood Genital Lichen Sclerosus

STUDY Ultrapotent Topical Corticosteroid Treatment of Childhood Genital Lichen Sclerosus

Maria C. Garzon, MD; Amy S. Paller, MD

Objective: To observe the clinical effects of short- Main Outcome Measure: Improvement of ery- term application of ultrapotent topical corticosteroid on thema, whitening erosions, and atrophy. Subjective im- symptomatic genital lesions of lichen sclerosus in pedi- provement of symptoms. atric patients. Results: All patients showed partial or total subsis- Design: Case series of 10 prepubertal girls with genital tence of signs and symptoms of lichen sclerosus. Fre- lichen sclerosus. Ultrapotent topical corticosteroids were quency and severity of recurrences varied, but patients applied twice daily for 6 to 8 weeks and patients were responded within a few days to reapplication of ultrapo- reexamined at completion of treatment. Long-term fol- tent topical corticosteroid. No significant adverse effects low-up over 6 months to 3 years. were noted after the initial 6- to 8-week course of therapy or during the 6-month to 3-year follow-up Setting: Pediatric dermatology clinic (referral center). period.

Patients: Ten prepubertal girls with typical clinical fea- Conclusion: A 6- to 8-week course of ultrapotent topi- tures of genital and/or perianal lichen sclerosus. cal corticosteroid is a safe and effective treatment for genital lichen sclerosus in pediatric patients. Intervention: Topical ultrapotent corticosteroid ointment was applied sparingly to affected areas for 6 to 8 weeks. Arch Dermatol. 1999;135:525-528

ICHEN SCLEROSUS is a chronic lier studies2,5 noted remission of the lichen skin disorder of unknown sclerosus in 80% of patients by puberty. cause that most commonly Others6,7 have described persistent evi- occurs in adult women. dence of the disorder (pallor, atrophy, or However, 10% to 15% of loss of tissue) in 89% to 97% of patients, casesL arise during childhood,1 and al- but resolution of symptoms in most pa- most always affect the genital area. Only tients. 6% of pediatric patients with lichen scle- The increased risk of vulvar squa- rosus have extragenital involvement.2 The mous cell carcinoma in association with li- disease occurs much more frequently in chen sclerosus in adult women is well girls than in boys, with a reported female- known. Subsequent development of ma- male ratio as high as 10:1.2-4 The associ- lignancy in adolescents with vulvar lichen ated symptoms, particularly pruritus, pain, sclerosus is a rare occurrence but has been dysuria, and constipation with pain on def- reported.8 In contrast, 18% of children de- ecation, may be chronic and are often dis- velop other long-term sequelae, including ruptive. Because of the location of le- scarring, adhesions, and atrophy.2,3,6,7,9 sions, discomfort, and signs of localized The treatment of lichen sclerosus in From the Departments of purpura with bleeding and discoloration, pediatric patients has been largely unsat- Dermatology and Pediatrics, lichen sclerosus in children may be mis- isfactory. Mild-potency topical corticor- College of Physicians & diagnosed as child abuse or as a genital in- steroids and bland emollients may re- Surgeons of Columbia fection. The course in children is vari- duce pruritus but generally do not alter the University, New York, NY (Dr Garzon); and the able, with some experiencing spontaneous course of the disease. Topical testoster- Departments of Pediatrics and remission, while others show persistence one has been used by some physicians; Dermatology, Northwestern of signs and symptoms in adulthood. How- however, concerns about virilization make University Medical School, ever, most reports suggest that affected pa- this an unacceptable treatment in the pe- Chicago, Ill (Dr Paller). tients improve significantly at puberty. Ear- diatric population. Moreover, controlled

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PATIENTS AND METHODS CASE 1

Patients were evaluated in the Pediatric Dermatol- A 6-year-old girl with a history of perianal fissuring pre- ogy Clinic of Children’s Memorial Hospital in Chi- sented with vaginal erythema, erosions, and discharge. cago, Ill. All patients in the study had typical clini- Physical examination revealed vulvar and perianal ery- cal features of lichen sclerosus at the onset of therapy. thema with superficial erosions and purulent discharge. These included the presence of whitening, atrophy, Bacterial cultures yielded group A ␤-hemolytic strepto- erythema, erosions, and purpura in a perineal and cocci. She was treated with a combination antibiotic of perianal distribution. Skin biopsy was thought to be amoxicillin-clavulanic acid and topical gentamicin with unnecessary in the presence of characteristic clini- some improvement. Follow-up examination revealed cal features in this age group. Parents were coun- whitening, purpura, and erosions consistent with li- seled about the unpredictable course of lichen sclerosus, potential adverse effects associated with therapy, chen sclerosus. She was treated with 0.05% betametha- and proper application of the topical corticosteroid. sone dipropionate ointment (Diprolene) applied twice Ultrapotent topical corticosteroid ointment with daily for 8 weeks with subsidence of symptoms and im- 0.05% clobetasol (Temovate), 0.05% diflorasone di- provement of her physical examination. During a acetate (Psorcon), 0.05% betamethasone dipropio- 2-year follow-up period she has developed intermittent nate (Diprolene), or betamethasone dipropionate recurrences, but a 2-day course of treatment with 0.05% without propylene glycol (Maxivate) was applied spar- betamethasone ointment clears the lesions. No evi- ingly twice daily to involved areas for 6 weeks. Pa- dence of steroid-induced atrophy or telangiectasia has tients were instructed to apply a “small pea- developed. sized”amount of corticosteroid at each application. The children were reexamined after completing the initial course of treatment. The course after initial ap- CASE 2 plication and possible long-term adverse effects during the subsequent 1 to 3 years were monitored by An 11-year-old girl with a history of vulvar and perianal reexamination and telephone follow-up (6 patients, lichen sclerosus presented to the clinic for treatment. reexamination; 4 patients, telephone follow-up). Physical examination showed whitening, atrophy, erythema, and erosions of the labia majora and introitus. The perianal area was whitened and fissured. She was treated with 0.05% diflorasone diacetate ointment, the use of studies show topical testosterone is no more effective than which was discontinued after several days of treatment vehicle for treatment of lichen sclerosus.10 Topical pro- because of increased erythema and discomfort. A change gesterone has been reported to be successful in a limited in therapy to 0.05% bethamethasone ointment resulted number of pediatric patients.11 Recently, topical reti- in significant improvement. After 6 weeks of treatment noid therapy has been of some benefit for the treatment her symptoms had completely resolved. Physical exami- of lichen sclerosus in adult women; however, pro- nation continued to show whitening and focal purpura; longed therapy is required to induce remissions.12 The however, erosions, fissuring, and erythema had re- effectiveness of this treatment and potential for irrita- solved. Over a 21-month follow-up period she had 4 mild tion remains to be determined in pediatric patients. flares of lichen sclerosus that were treated for 3 to 5 days Studies performed in adult women with vulvar li- with betamethasone ointment. No evidence of steroid- chen sclerosus have demonstrated that twice daily ap- induced adverse effects has been noted. plication for 6 to 12 weeks of 0.05% clobetasol propionate ointment, an ultrapotent topical corticosteroid, is a CASE 3 safe and effective treatment. In these studies, patients were noted to have both clinical and histological improve- A 9-year-old girl was referred to our clinic with a his- ment of their skin lesions without the occurrence of sig- tory of vulvar lichen sclerosus that did not improve with nificant adverse effects from the topical corticosteroids. topical progesterone treatment or topical hydrocorti- These patients were subsequently able to control their sone. Examination showed that she had whitening and symptoms with the intermittent use of a lower-potency erosions of the vulvar and perianal area. She also had nu- topical corticosteroid that was previously ineffective, or merous atrophic white macules with follicular plugging occasional use of the ultrapotent topical corticosteroid. on her upper chest and back. We initiated 0.05% beta- Ultrapotent topical corticosteroid application was more methasone ointment for treatment of the lesions. The pa- effective and resulted in fewer adverse effects than topi- tient complained of pain associated with application of cal testosterone or topical progesterone therapy.13-16 The the ointment and was switched to another preparation use of ultrapotent topical corticosteroids for children with of 0.05% betamethasone ointment that did not contain genital lichen sclerosus has rarely been described, and propylene glycol. This was well tolerated and on fol- concerns about the risk of associated cutaneous adverse low-up at 6 weeks her discomfort had resolved. Physi- effects have limited its routine use.6,17-21 We investigated cal examination revealed improvement, but mild whit- the efficacy and safety of treatment of genital lichen scle- ening and atrophy persisted. The truncal lesions remained rosus with a 6-week course of twice daily application of unchanged with treatment. She experienced 1 flare dur- ultrapotent topical corticosteroid. ing the subsequent 20 months, which responded to ap-

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 plication of a propylene glycol–free preparation of 0.05% betamethasone ointment. Childhood Genital Lichen Sclerosus: Patient Characteristics*

RESULTS Weeks of Total Age at Age at Treatment/ Follow-up, No. of Ten children with lichen sclerosus were enrolled in the Patient No. Onset, y Treatment, y Drug No. of mo Relapses Table study, ranging in age from 2.5 to 11.5 years ( ). Ten 1 4 6 8/bd 26 6 girls with genital and/or perianal lichen sclerosus were 2 4 11.5 6†/dd, bd 21 4 treated with an initial 6-week course of topical ultrapo- 3 5 9 7†/bd, dd, bp 20 1 tent corticosteroid ointment. For most patients, the cor- 4 2.5 2.5 6/cp 13 0 rect diagnosis was made in the dermatology clinic. The 5 3.5 4.5 8/cp 36 3 duration of symptoms of lichen sclerosus before initiat- 6 4 7 5†/cp 15 0 ing treatment ranged from several weeks to more than 7 7 5 5 6/cp 16 0 8 7 8.5 6†/cp; 4/dd 5 0 years. Pruritus, chronic discomfort, dysuria, and pain with 9 8 8 6/cp 15 Many defecation were common chief complaints in our pa- 10 5 6 8/bd 4 2 tients. Previous application of nonfluorinated corticosteroids (eg, hydrocortisone) or other topical medica- *Bd indicates betamethasone dipropionate ointment (Diprolene); dd, 0.05% tions (eg, antibacterial ointments, antifungal creams, or diflorasone diacetate ointment (Psorcon); bp, 0.05% betamethasone dipropionate ointment without propylene glycol (Maxivate); and cp, 0.05% bland emollients) had resulted in no significant or per- clobetasol propionate ointment (Temovate). sistent improvement. Most patients had perianal and vul- †Patients complained of burning with initial ultrapotent corticosteroid var involvement in the classic “figure eight” or “key- preparation. hole” distribution. One of the 10 children (patient 3) had extragenital involvement with truncal lesions. though extragenital sites may also be involved.3,7 In chil- All children demonstrated clinical improvement of dren, symptoms usually begin between 3 and 7 years of their symptoms and skin lesions on follow-up examina- life.7 Dysuria, pruritus, constipation, and pain are com- tion. Four of the 10 girls showed improvement but were mon presenting complaints. As shown in the selected cases not clear after 6 weeks, and they showed further im- described, the recognition of lichen sclerosus in chil- provement after treatment with corticosteroid for an ad- dren is poor among primary care physicians and even ditional 2 weeks. among specialists. Four girls complained of irritation and burning and Most commonly, affected children are erroneously overall initial worsening with application of ultrapotent thought to have bacterial or, less commonly, yeast vagi- topical steroid. One patient who experienced burning from nitis, and are treated with several topical and systemic use of topical corticosteroid continued application of the antibiotics before referral is made. It should be realized, clobetasol that was initially prescribed (patient 6). She however, that secondary bacterial or yeast infection may was examined 5 weeks after initiation of the treatment, occur, as seen in case 1. In a British study,22 bacterial cul- and application of the topical corticosteroid was discon- tures from the genital area of children with lichen scle- tinued because the signs of lichen sclerosus had almost rosus yielded organisms in 56% of 42 affected girls. Strep- cleared despite the burning sensation. The ultrapotent tococcus was cultured from the area in 21% of the patients, topical corticosteroid preparation was changed in the other while Escherichia coli and Staphylococcus were found in 3 girls, and in 2 of them (patients 2 and 8) the second 10% and 7% of patients, respectively. Candida albicans corticosteroid preparation was tolerated well. In the third was detected in 1 patient. Secondary bacterial infections girl (patient 3), burning was experienced with the ap- may show intense erythema, increased discomfort, and plications of both betamethasone and diflorasone, but she purulent drainage; candidal infections tend to be asso- tolerated the betamethasone ointment without propyl- ciated with increased erythema. If infection is sus- ene glycol, suggesting the occurrence of either reaction pected, cultures should be performed to verify the pres- to the propylene glycol or perhaps spontaneous subsidence of bacterial or candidal organisms, and appropriate ence of the inflammatory response after 2 weeks of antibiotic therapy should be initiated before administra- therapy. tion of topical corticosteroid therapy for the underlying The duration of further follow-up varied from 4 to lichen sclerosus. 36 months after completing the initial course of therapy. Patients with lichen sclerosus may present with se- All reported overall significant subjective improve- vere pain with defecation and/or urination that leads to ment; however, 6 girls were noted to have recurrences gastroenterology or urology referral, respectively, with that were described as mild, and responded to brief courses generally ineffective management unless the underlying (2 days to 1 week) of ultrapotent topical steroid appli- cause is recognized. The other frequent misdiagnosis for cation. No steroid-induced atrophy or telangiectasias were patients with lichen sclerosus is child abuse, with par- noted on follow-up examinations. ents accused on the basis of the symptoms of pain and pruritus, and the clinical signs of bleeding, erosion, and COMMENT discoloration of the genital area. On the other hand, a diagnosis of lichen sclerosus does not rule out the pos- Lichen sclerosus is an inflammatory condition of un- sibility of concomitant sexual abuse.22 known cause that most commonly affects the genital skin The lesions of lichen sclerosus in children are of- of prepubertal girls and postmenopausal women, al- ten associated with considerable burning pain requires

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 intervention. Treatment of childhood lichen sclerosus has treatment for vulvar and perianal lichen sclerosus in been difficult. Application of bland emollients and mild- children. Continuing observation every 6 to 12 months potency topical corticosteroids has been the mainstay of is important to monitor for recurrences. Further study therapy. These treatments are often only partially effec- is needed to assess the safety of long-term therapy that tive. Local application of hormones has been reported to may be necessary to prevent scarring that is associated be effective in some patients. Progesterone may be effec- with recurrence. tive in some patients. Its use has been limited in children because of concerns about potential adverse ef- Accepted for publication July 21, 1998. fects associated with hormonal therapy. Topical Corresponding author: Maria C. Garzon, MD, De- testosterone has been found to be no more effective than partment of Dermatology, Columbia University, 161 Fort petrolatum for the treatment of this disorder.10 Ultrapo- Washington Ave, New York, NY 10032 (e-mail: tent topical corticosteroid application has been the most [email protected]). effective and well-tolerated therapy for adults with this disorder. REFERENCES We reviewed our experience using ultrapotent topi-

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Genital lichen sclerosus (lichen sclerosus et atrophicus) in child- 17 hood and adolescence. J R Soc Med. 1993;86:69-75. though Fischer and Rogers have recently described labial 7. Redmond CA, Cowell CA, Krafchick BR. Original studies: genital lichen sclero- telangiectasia in 18% of 11 pediatric patients with li- sus in prepubertal girls. Adolesc Pediatr Gynecol. 1988;8:97-101. chen sclerosus treated with clobetasol. Four of our pa- 8. Caro GM, Paradinas FJ. Squamous cell carcinoma of the vulva in association with tients complained of burning with application of ini- mixed vulvar dystrophy in an 18 year old girl: case report. Br J Obstet Gynecol. tially applied ultrapotent coritcosteroid ointment, 1984;91:87-90. 9. Helm KF, Gibson LE, Muller SA. Lichen sclerosus et atrophicus in children and associated with increased erythema and edema at sites young adults. Pediatr Dermatol. 1991;8:97-101. of application. In 3 of these patients, therapy was changed 10. Sideri M, Origoni M, Spinanci L, et al. Topical testosterone in the treatment of after 1 to 2 weeks to an alternate ultrapotent topical cor- vulvar lichen sclerosis. Int J Gynaecol Obstet. 1994;46:53-56. ticosteroid ointment. The frequency of this reaction, even 11. Serrano G, Millan F, Fortea JM, et al. Topical progesterone as a treatment of choice in genital lichen sclerosus et atrophicus in children. Pediatr Dermatol. 1993;10: though the particular potent corticosteroid preparation 201. varied, made us consider the possibility that the mecha- 12. Virgili A, Corazza M, Bianchi A, et al. Open study of topical 0.025% tretinoin in nism of corticosteroid action involved a burst of re- the treatment of vulvar lichen sclerosus. J Reprod Med. 1995;46:614-618. leased mediators of inflammation, which ultimately re- 13. Dalziel KL, Millard P, Wojnarowska F. The treatment of vulval lichen sclerosus sulted in improvement and sometimes resolution of the with a very potent topical steroid (clobetasol propionate 0.05%). Br J Dermatol. 1991;124:461-464. lichen sclerosus. In the long-term follow-up study by Dal- 14. Dalziel KL, Wojnarowska F. Long-term control of lichen sclerosus with a potent 14 ziel and Wojnarowska of 12 adult women treated with topical steroid cream. J Reproduct Med. 1993;38:25-27. 0.05% topical clobetasol cream, 2 patients experienced 15. Bracco GL, Carli P, Sonni L, et al. Clinical and histologic effects of topical treat- burning and discomfort with application. One patient de- ments of vulval lichen sclerosus: a critical evaluation. J Reprod Med. 1993;38: veloped complaints after initially tolerating treatment but 37-40. 16. Carli P, Cattaneo A, Giannotti B. Clobetasol propinoate 0.05% cream in the treat- was found to have a contact sensitivity to the prepara- ment of vulvar lichen sclerosus: effect on the immunohistochemical profile. Br J tion on patch testing. No contact sensitivity could be de- Dermatol. 1992;127:542-543. termined to the topical corticosteroid or to the vehicle 17. Fischer G, Rogers M. Treatment of childhood vulvar lichen sclerosus with po- in the second patient. Our patients did not undergo patch tent topical corticosteroid. Pediatr Dermatol. 1997;14:235-238. 18. Krafchik BR. Advances in vulvar disease: lichen sclerosus et atrophicus et al. Adv testing, but contact dermatitis to propylene glycol may Dermatol. 1991;7:163-177. have caused the reaction in patient 3. Further observa- 19. Berth-Jones J, Graham-Brown RAC, Burns DA. Lichen sclerosus et atrophicus: tion of children receiving this therapy needs to be un- a review of 15 cases in young girls. 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