Australasian Journal of Dermatology (2016) 57, 39–43

doi: 10.1111/ajd.12305

SMALL CASE SERIES

Fractional carbon dioxide laser in recalcitrant vulval lichen sclerosus Andrew Lee,1,2 Adrian Lim1,3 and Gayle Fischer1,2 1

Department of Dermatology, Royal North Shore Hospital, 2Northern Clinical School, University of Sydney, St Leonards, and 3uRepublic Cosmetic Skin & Laser Clinic, Sydney, New South Wales, Australia

ABSTRACT Vulval lichen sclerosus is an uncommon skin condition that can usually be managed with topical corticosteroids to maintain remission. However, there is a subset of patients in whom it remains recalcitrant despite treatment with super-potent topical corticosteroids. We report a case series of four patients undergoing fractional carbon dioxide laser resurfacing and one with ablative carbon dioxide laser for severe, hyperkeratotic vulval lichen sclerosus not responding to super-potent topical corticosteroids. In these patients, carbon dioxide laser was successful in achieving remission. Their vulval lichen sclerosus was subsequently able to be maintained with topical corticosteroid treatment. Key words: carbon dioxide laser, fractional CO2, lichen sclerosus, vulvar lichen sclerosus.

INTRODUCTION Vulval lichen sclerosus (VLS) is an uncommon but important chronic skin condition that usually requires lifelong management to maintain remission.1 A minority of patients are asymptomatic but most report significant itch, discomfort and dyspareunia. Left untreated it has significant potential to result in the destruction of the vulval architecture and less commonly has been clearly associated with squamous cell carcinoma (SCC) of the vulva.2,3 Most patients can be managed effectively with a topical corticosteroid regimen.1 There is, however, a subset of patients with hyperkeratotic

Correspondence: Dr Andrew Lee, Dermatology Research Office, Level 2, Building 52, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065, Australia. Email: [email protected] Andrew Lee, MBBS. Adrian Lim, FACD. Gayle Fischer, FACD. Conflict of interest: none Submitted 19 November 2014; accepted 15 December 2014. © 2015 The Australasian College of Dermatologists

disease in whom VLS remains recalcitrant despite treatment with super-potent topical corticosteroids. There have been previous reports that carbon dioxide (CO2) laser may be an effective form of treatment for patients with genital lichen sclerosus in both men and women. We report a case series of patients undergoing fractional CO2 laser resurfacing for severe, hyperkeratotic VLS not responding to superpotent topical corticosteroid.

PATIENTS AND METHODS Five women with severe hyperkeratotic VLS were recruited from the rooms of a private dermatology clinic. All had biopsy-confirmed VLS. All had been previously treated with the super-potent topical corticosteroid clobetasol propionate 0.05% ointment with limited efficacy, evidenced by ongoing symptoms and the lack of an objective response to treatment. In some cases the entire area of lichen sclerosus was unresponsive to treatment while for others there were particular areas on the vulva that remained recalcitrant. None had a history of vulval intraepithelial neoplasia or SCC of the vulva. Two patients were premenopausal and three were post-menopausal. None was on oral or topical hormone replacement therapy. Four patients were symptomatic prior to treatment with itch and dyspareunia and one patient was asymptomatic. The clinical distribution of the lichen sclerosus varied and is summarised in Table 1, along with other relevant patient details. Our index case (Case 1) was unresponsive to super-potent corticosteroids. However, it was noticed that the site of her diagnostic biopsy healed and then remained free of VLS. She had significant ongoing dyspareunia associated with unresponsive LS. Based on the hypothesis that epithelial ablation might achieve the same result on the rest of her vulva she agreed to referral to a gynaecological oncologist for ablative CO2 laser. She had a dramatic response (Figs 1,2), although she experienced significant discomfort for 2 weeks after the procedure. She subsequently became

Abbreviations: SCC VLS

squamous cell carcinoma vulval lichen sclerosus

24

Vulva Yes Itch, dyspareunia 1 Complete No No 12 Clobetasol

12

Vulva No Itch, dyspareunia 1

Complete No

No 48

Clobetasol

Duration of treatment with TCS without response (months) Distribution Loss of architecture Symptoms No of treatments with CO2 laser Symptom resolution Progress of adhesions/ scarring Requiring further laser? Duration of follow up (months) Maintenance treatment

© 2015 The Australasian College of Dermatologists

Clobetasol

Yes 9

Complete No

Figure of 8 Yes Itch, dyspareunia 3

12

60 Caucasian Yes No No Clobetasol propionate 0.05% ointment

Case 3

HRT, hormone replacement therapy; SCC, squamous cell carcinoma; TCS, topical corticosteroid.

39 Indian No No No Clobetasol propionate 0.05% ointment; methylprednisolone aceponate 1% ointment

60 Caucasian Yes No No Clobetasol propionate 0.05% ointment; betamethasone dipropionate 0.05% ointment in optimised vehicle

Age Ethnicity Menopause HRT SCC Previous treatment

Case 2

Case 1

Clinical data of patients with CO2 laser of vulval lichen sclerosus

Characteristic

Table 1

Clobetasol

Yes 6

No change No

Perineum Yes None 2

36

65 Caucasian Yes No No Clobetasol propionate 0.05% ointment; betamethasone dipropionate 0.05% ointment in optimised vehicle

Case 4

Clobetasol

No 6

Partial No

Inner labia minora Yes Itch, dyspareunia 1

56 Caucasian No No No Clobetasol propionate 0.05% ointment; betamethasone dipropionate 0.05% ointment in optimised vehicle, methylprednisolone aceponate 1% ointment 30

Case 5

40 A Lee et al

CO2 laser and vulval lichen sclerosus

Figure 1

41

Case 1, before CO2 laser.

Figure 3

Case 3, before CO2 laser.

affected area was treated with two passes with additional two passes applied focally to more hypertrophic areas. Transient whitening of the treated skin occurred with each pass and repeat passes were delivered without intervening tissue wipes. All patients tolerated the procedure very well with topical anaesthesia and chilled air delivery system (Cryo-jet [Seoul, South Korea]).

RESULTS

Figure 2

Case 1, 12 months after CO2 laser.

asymptomatic and relapse was prevented with topical clobetasol 0.05% ointment. Following this, a decision was made to continue trialling CO2 laser treatment for cases of severe recalcitrant VLS, using a fractional CO2 laser method which would be potentially better tolerated but as effective. Henceforth, the remainder of our patients were seen by a dermatologist for fractional CO2 laser treatment according to the following methods: prophylactic cephalexin and acyclovir were given to the patients commencing a day before laser therapy and continued for 4 days post-treatment. On the day of treatment, compound topical anaesthesia (23% lignocaine, 7% tetracaine in anhydrous gel) was applied to the lesion sites for 1 hour prior to the procedure. The patients were then treated with carbon dioxide laser (Lumenis AcuPulse, 40W [Lumenis, Melbourne, Australia]) on superficial fractional mode with the following parameter: 140–170MJ energy (treatment depth of 150 μm), 10 mm hexagonal scan size, at 60% density per pass. The

The mean age of the participants was 56 years (range, 39–65 years). Two out of the five patients experienced significant discomfort that lasted up to a week following the CO2 laser. Consequently, the next three patients who underwent the procedure were advised to take simple prophylactic analgesia with paracetamol and ibuprofen for a couple of days after the procedure. These three patients did not report any significant discomfort. No other side-effects such as infection or bleeding were encountered. Re-epithelialisation occurred within 3–4 weeks in all cases. The four patients who reported being symptomatic prior to CO2 laser all reported subjective improvements post CO2 laser. The one patient who reported being asymptomatic reported no change. All five women were able to return to maintenance treatment with clobetasol 0.05%, which was effective in maintaining clinical remission of their VLS in the follow-up period. Two patients required more than one treatment, as we found that CO2 was very effective in suppressing hyperkeratosis clinically initially, but that hyperkeratosis recurred after 6–8 months (Figs 3,4). In between the CO2 laser treatments the patients were managed with 0.05% clobetasol. At the time of writing the VLS of all patients remained well controlled at follow up.

DISCUSSION VLS is in most cases responsive to treatment with superpotent topical corticosteroid, which has been shown in © 2015 The Australasian College of Dermatologists

A Lee et al.

42

Figure 4

Case 3, 6 months after third CO2 laser.

many studies to be the standard of care.1,4,5 In our experience, treatment resistance usually occurs where the disease is severe and hyperkeratotic, and in such cases prolonged treatment with super-potent corticosteroid may be ineffective, even over long periods of treatment. CO2 laser treatment of penile lichen sclerosus (Balanitis xerotica obliterans) was first described by Rosemberg and Jacobs in 1982.6 In this single case report their patient had improved function, cosmetic appearance and minimal postoperative discomfort following CO2 vaporisation. Since then a number of case studies and reports have shown that CO2 laser therapy is an effective form of treatment in Balanitis xerotica obliterans.7–9 Previous reports of CO2 laser treatment in women with VLS have shown mixed results. In a case series of seven women with VLS, six patients refractory to other treatment became asymptomatic following laser ablation.10 In 1997 it was reported that CO2 laser treatment in two women for VLS was effective in treating genital lesions, although the disease recurred. No follow-up treatment was given in these cases.7 Another case report of two women with VLS unresponsive to topical clobetasol propionate 0.05% became asymptomatic for a prolonged duration (2–3 years) with normal re-epithelisation of the vulval tissue following CO2 laser treatment and with no further follow-up treatment.11 Our study supports previous reports, with three patients responding very well to single session CO2 laser treatment and two patients requiring multiple treatments before their disease remitted. After the treatment it was then possible to maintain improvement with a super-potent topical corticosteroid in all patients. At the time of writing the patients have remained well over a follow-up period between 6 months to 4 years. With our laser resurfacing approach to VLS, we opted for high density – low energy/depth for two reasons. Firstly, lichen sclerosus is clinically atrophic and sclerotic, with areas of hyperkeratosis, and therefore we feel that greater coverage (density) is more important than treatment depth. The other consideration is the patients’ comfort under © 2015 The Australasian College of Dermatologists

topical anaesthesia, which may not be as easily accomplished with low density – high energy/depth parameters. However, we acknowledge that the latter option (low density – high energy/depth) can be explored down the line. We feel that our selected parameters effectively attain an equilibrium between procedural comfort, recovery time and efficacy. The mechanism of action of the CO2 laser is via the absorption of light energy by water molecules within the epidermis, which leads to heat accumulation and the subsequent ablation of the epidermis and superficial dermis.12 The fractional element of the CO2 laser as used in our study function by the creation of numerous microscopic thermal zones in which there is ablated skin.13,14 Two passes of superficial fractional CO2 at 60% density approaches the coverage of full resurfacing with the added benefit that the procedure is well tolerated under topical anaesthesia. Prior to treatment lichen sclerosus is histologically characterised by dermal inflammation and hyalinisation. Fractional CO2 laser treatment not only ablates the hyperkeratotic epidermis but also has a residual thermal effect on the underlying dermis. The dermis in patients with lichen sclerosus, especially near the dermal-epidermal junction, can theoretically be characterised by dysregulated signalling. As a result, there may be upregulation of α3β1 integrin, which in turn stimulates MAP-kinase, which promotes epidermal migration and therefore hyperkeratosis of the epidermis.15,16 Subsequent re-epithelisation is characterised by the reduction of hyperkeratosis, which in turn enhances topical corticosteroid efficacy. This reduction in hyperkeratosis may be explained by the CO2 laser ablating the improperly function dermal-epidermal zone, creating a new zone that functions properly. This then allows for maintenance and the continued remission of the lichen sclerosus. We achieved this in our study with the use of 0.05% clobetasol propionate ointment.

CONCLUSION We report a series of women with severe, treatmentresistant hyperkeratotic VLS recalcitrant to topical corticosteroid treatment; four of whom responded positively to fractional CO2 laser treatment, and one to ablative CO2 laser therapy. This allowed the subsequent control of the disease with topical therapy. The fractional CO2 laser, although invasive, was well tolerated without adverse effects other than post-operative pain and may be an adjunctive option to gain control of this condition in women with hyperkeratotic disease, although in all patients follow up with a super-potent topical steroid was instituted to ensure that they remained in remission.

REFERENCES 1.

2.

Bradford J, Fischer G. Long-term management of vulval lichen sclerosus in adult women. Aust. N. Z. J. Obstet. Gynaecol. 2010; 50: 148–52. Carli P, Cattaneo A, De Magnis A et al. Squamous cell carcinoma arising in vulval lichen sclerosus: a longitudinal cohort study. Eur. J. Cancer Prev. 1995; 4: 491–5.

CO2 laser and vulval lichen sclerosus 3. 4.

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8. 9.

Scurry JP, Vanin K. Vulvar squamous cell carcinoma and lichen sclerosus. Australas. J. Dermatol. 1997; 38 (Suppl. 1): S20–5. Neill S, Lewis FM, Tatnall FM et al. British Association of Dermatologist’ guidelines for the management of lichen sclerosus 2010. Br. J. Dermatol. 2010; 163: 672–82. Renaud-Vilmer C, Cavelier-Balloy B, Porcher R et al. Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch. Dermatol. 2004; 140: 709–12. Rosemberg SK, Jacobs H. Continuous wave carbon dioxide treatment of balanitis xerotica obliterans. Urology 1982; 19: 539–41. Kartamaa M, Reitamo S. Treatment of lichen sclerosus with carbon dioxide laser vaporization. Br. J. Dermatol. 1997; 136: 356–9. Ratz JL. Carbon dioxide laser treatment of balanitis xerotica obliterans. J. Am. Acad. Dermatol. 1984; 10: 925–8. Windahl T, Hellsten S. Carbon dioxide laser treatment of lichen sclerosus et atrophicus. J. Urol. 1993; 150: 868–70.

10. 11.

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Stuart GC, Nation JG, Malliah VS et al. Laser therapy of vulvar lichen sclerosus et atrophicus. Can. J. Surg. 1991; 34: 469–70. Peterson CM, Lane JE, Ratz JL. Successful carbon dioxide laser therapy for refractory anogenital lichen sclerosus. Dermatol. Surg. 2004; 30: 1148–51. Brightman LA, Brauer JA, Anolik R et al. Ablative and fractional ablative lasers. Dermatol. Clin. 2009; 27: 479–89. Bogdan Allemann I, Kaufman J. Fractional photothermolysis – an update. Lasers Med. Sci. 2010; 25: 137–44. Hantash BM, Bedi VP, Chan KF et al. Ex vivo histological characterization of a novel ablative fractional resurfacing device. Lasers Surg. Med. 2007; 39: 87–95. Jost M, Huggett TM, Kari C et al. Matrix-independent survival of human keratinocytes through an EGF receptor/MAPKkinase-dependent pathway. Mol. Biol. Cell 2001; 12: 1519–27. Manohar A, Shome SG, Lamar J et al. Alpha 3 beta 1 integrin promotes keratinocyte cell survival through activation of a MEK/ERK signaling pathway. J. Cell Sci. 2004; 117 (Pt 18): 4043–54.

© 2015 The Australasian College of Dermatologists

Fractional carbon dioxide laser in recalcitrant vulval lichen sclerosus.

Vulval lichen sclerosus is an uncommon skin condition that can usually be managed with topical corticosteroids to maintain remission. However, there i...
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