Treatment Modalities for Genital Lichen Sclerosus: A Systematic Review
Abstract
:1. Introduction
2. Methods
2.1. Search Strategy, Study Eligibility Criteria, and Study Selection
2.2. Data Extraction and Synthesis
3. Results
3.1. Study and Patient Characteristics
3.2. Risk of Bias
3.3. Topical Corticosteroids as a Single Modality
3.4. Topical Corticosteroids and Adjunct Agents
3.5. Steroid-Sparing Topical Agents
3.6. Intradermal Injections
3.7. Energy-Based Devices
3.8. Oral Therapies
3.9. Psychological Counselling
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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# Patients | Mean Age (Age Range) | Affected Region | Treatment Modality | Response | Adverse Events | Follow Up Duration | Remission or Relapse | Risk of Bias | |
---|---|---|---|---|---|---|---|---|---|
Topical Steroids as a Single Modality | |||||||||
Corazza 2016 [15] | 48 | 64.14 (NR) | Vulva | Group 1 (24): Clobetasol propionate 0.05% ointment twice weekly for 52 weeks (CP) Group 2 (24): Mometasone furoate 0.1% ointment twice weekly for 52 weeks (MF) | Mean change in features:
| None | 52 weeks | 3 cases of relapse: 2 in CP, 1 in MF Mean time to relapse: 30 weeks (range 20–38) | Some concern |
Virgili 2014 [16] | 54 | 64.2 (NR) | Vulva | Group 1 (27): Clobetasol propionate 0.05% ointment five days per week for 4 weeks, then on alternate days for 4 weeks, then twice weekly for 4 weeks (CP) Group 2 (27): Mometasone furoate 0.1% ointment five days per week for 4 weeks, then on alternate days for 4 weeks, then twice weekly for 4 weeks (MF) | CP:
MF:
| None | 12 weeks | 24 patients responded, while 1 did not for CP 24 patients responded, while 2 did not for MF | Some concern |
Borghi 2015 [17] | 64 | 60.95 (NR) | Vulva | Group A (32): Mometasone furoate 0.1% ointment daily for 5 days per week for 4 weeks, then on alternate days for 4 weeks, then twice weekly for 4 weeks Group B (32): Mometasone furoate 0.1% ointment 5 days weekly |
| None | 12 weeks | 27 responders and 4 non-responders in MF1 25 responders and 4 non-responders in MF2 | Some concern |
Virgili 2013 [18] | 27 | 60.53 (NR) | Vulva | Treatment Phase (12 weeks):
Maintenance Phase (52 weeks), whereby all patients were assigned to one modality:
| Treatment Phase (27 patients):
Maintenance Phase (25 patients):
| None | 64 weeks | MF: 7 remission, 0 relapse VitE: 4 remission, 5 relapse CC: 3 remission, 5 relapse Median time to relapse for VitE and CC: 21.6 weeks | Some concern |
Topical Corticosteroids and Adjunct Therapies | |||||||||
D’Antuono 2011 [19] | 42 | 51.5 (22–79) | Vulva | Treatment Phase (6 months):
| CT Group:
DS Group:
| 3 cases of Candida vulvovaginitis in CT group | 6 months | CT: Remission in 0 patients, relapse not noted DS: Remission in 2 patients, relapse not noted | Some concern |
Non-Steroid Topicals | |||||||||
Cattaneo 1996 [14] | 32 | 60 (28–85) | Vulva | First part of treatment (32):
Second part of treatment:
| First part of treatment:
Second part of treatment:
| Burning (4) and itching (9) on application of testosterone ointment | 48 weeks | Symptomatic relief in all patients in first phase Worsening of symptoms in patients in TP arm of study 3 patients maintained on placebo improved | Low concern |
Funaro 2014 [20] | 55 | 46.6 (NR) | Vulva | Group 1 (28): Tacrolimus 0.1% ointment daily for 3 months (CL) Control group (27): Clobetasol propionate 0.05% ointment daily for 3 months (CP) |
| None | 3 months | Remission in 9/28 (32%) of CP patients, only 19/27 (70%) of TL patients | Low concern |
Goldstein 2011 [21] | 38 | NR (NR) | Vulva | Group 1 (17): Pimecrolimus 1% cream twice daily for 12 weeks (PIM) Group 2 (19): Clobetasol propionate 0.05% cream twice daily for 12 weeks (CP) |
| None | 12 weeks | 26 patients completed the follow-up period, where 24 showed improvement and 11 (42%) experienced remission (not broken down by treatment arm) | Low concern |
Sideri 1994 [22] | 58 | 56.5 (35–83) | Vulva | Group 1 (30): 2% Testosterone propionate in Vaseline Group 2 (28): Petroleum ointment | Symptom improvement (pruritus vulvae, burning): Testosterone propionate group:
Placebo:
No significant difference found between groups. | n = 4, adverse events not specified | 12 months | Improvement in dystrophy in 17 patients (group not specified), but no histological demonstration of regression in any of the cases. | Low concern |
Gunthert 2022 [23] | 37 | 34.52 (NR) | Vulva | Group 1 (17): Progesterone 8% ointment, 2 g daily for 12 weeks (PRO) Group 2 (20): Clobetasol propionate 0.05% ointment, 2 g daily for 12 weeks (CP) | Change in:
| CP: Genital herpes (2), mycotic genital infection (1), urinary tract infection (2) PRO: Mycotic genital infection (1), vulvitis (2), urinary tract infection (1), peritonitis (1) | 24 weeks | Remission in 6/10 PRO patients, 13/16 CP patients | Low concern |
Bracco 1993 [24] | 79 | 57 (27–83) | Vulva | Group 1 (20): Clobetasol propionate 0.05% topical Group 2 (20): Testosterone 2% topical Group 3 (20): Progesterone 2% topical Group 4 (19): Cream-based preparation topical | Symptoms (itching, burning, pain and dyspareunia) were classified from 0–3, with 3 most severe. Symptom improvement:
Symptom unchanged:
Gross changes: Significant difference in clobetasol group only (p < 0.001, CI 2.93–4.97) Gross appearance mean score, clobetasol: 5.8 to 1.9 Histological evaluation: Significant difference in clobetasol group only (p < 0.001, CI 2.29–4.65), mean score 7.1 to 3.7 | None | 3 months | Symptom remission (no symptoms and/or lesions remaining): Clobetasol propionate: 75% Testosterone: 20% Progesterone: 10% Cream-based preparation: 10.5%. Follow up encouraged for an additional 3 months for clobetasol group, in which patients encouraged to use it twice weekly for 3 more months. Of remaining 13 patients, 11 continued good response to therapy, 2 who discontinued had recurrence. | Low concern |
Goldstein 2015 [25] | 30 | 58 (NR) | Vulva | Treatment Group (TG) (15): Human fibroblast lysate cream twice daily for 12 weeks Control Group (CG) (15): Placebo cream with the same emollient base as the treatment cream twice daily for 12 weeks |
| None | 12 weeks | No relapse noted | Some concern |
Virgili 2013 [26] | 80 | 61.85 (12.17–84.92) | Vulva | Maintenance therapy (following a 12-week active treatment phase on topical 0.1% mometasone furoate ointment daily; patients who achieved a symptomatologic VAS global score ≤ 5/30 and an IGA score ≤ 2 (total or almost total healing) were judged as “treatment responsive” and were eligible for the MP) with:
| Primary efficacy point: relapse rate at both week 26 and 52 Second efficacy variable: mean time to relapse, defined as number of weeks from start of maintenance phase (MP) until LS relapse Total cumulative crude relapse rate (intention to treat): 25% (20/80) Total cumulative modified crude relapse rate: 52.36% (20/38) Crude relapse rates after 52 weeks of maintenance treatment:
Median time to relapse:
| No observed adverse events | 52 weeks | Relapses
Dropouts (total n = 42):
| Low concern |
Intradermal Injections | |||||||||
Gutierrez-Ontalvilla 2022 [27] | 19 | 55.17 (NR) | Vulva | Treatment Group (TG) (9): 24 mL of nanofat mixed with PRP, 2 infiltrations 3 months apart Control Group (CG) (10): Topical clobetasol propionate 0.05% cream once or twice weekly | Mean change in feature, standard deviation within brackets:
| None | 12 months | 3 cases of relapse, all patients in control group | Some concern |
Goldstein 2019 [28] | 30 | 52.6 (NR) | Vulva | Group 1 (20): Platelet-rich plasma intradermal injections, separated by 6 weeks (PRP) Group 2 (10): Placebo saline injections (PLA) | Change in histopathologic inflammation:
Change in Clinical Scoring System for Vulvar LS: −7.74 in PRP, −9.44 in PLA, p = 0.654 | Bruising | 12 weeks | Not specified | Low concern |
Energy-Based Devices | |||||||||
Guo 2022 [29] | 50 | NR (NR) | Vulva | Experimental group: CO2 laser once monthly for 3 months (CO2) Control group 1: Radiofrequency treatment with 5-aminolevulinic acid as a photosensitizer once weekly for 10 weeks (RF) Control group 2: Clobetasol propionate 0.05% ointment with traditional Chinese medicine soaking and washing for 3–4 months, then once every other day for 4 weeks, then twice weekly for 4 weeks (CP) | Change in scores at 1 month after treatment:
Change in scores at 3 months after treatment:
| None reported | 3 months | Not specified | Some concern |
Burkett 2021 [30] | 52 | 64.5 (NR) | Vulva | Group 1 (19): Fractionated CO2 laser therapy, 5 courses 4–6 weeks apart (CO2) Group 2 (18): Clobetasol propionate 0.05% ointment nightly for 1 month, then three times weekly for 2 months, then as needed (CP) | Change in…
| Minor burning and blistering with CO2 (1); reactivation of genital herpes 1 week after starting CP (1) | 6 months | Not specified | Some concern |
Mitchell 2021 [31] | 37 | 59 (51–64) | Vulva | Group 1 (19): Fractionated CO2 laser therapy, 5 courses in 24 weeks (CO2) Group 2 (18): Placebo laser (PLA) | Change in…
| Transient, mild discomfort (n not specified) | 24 weeks | No remission achieved | Low concern |
Krause 2023 [32] | 67 | Low dose group: 53 (21–80) Normal dose group: 52 (20–79) | Vulva | Microablative CO2 laser low dose group (LDG) (29): three laser applications in three subsequent sessions of three weeks. Microablative CO2 laser normal dose group (NDG) (34): three laser applications in three subsequent sessions of three weeks. | Mean change in total VAS score at 18 weeks
Mean change in total LS score at 18 weeks:
Regarding sexual activity:
Regarding quality of life (QoL):
| Burning sensation during laser application, not requiring intervention: 31 No other adverse events or side effects reported. | 18 weeks | No reported relapses or remissions. | Low concern |
Bizjak Ogrinc 2019 [33] | 40 | 58 (NR) | Vulva | Experimental group (20): 3 neodymium-doped yttrium aluminium garnet (Nd:YAG) laser treatments every 14 days (Nd:YAG) Control group (20): Topical betamethasone twice daily for 2 weeks, then once daily for one week, then every second day for one week (BM) | Change in scores at 3 months after treatment:
Change in scores at 6 months after treatment:
| None | 6 months | 8/20 Nd:YAG-treated patients were free of symptoms at 3-month follow up, compared with none of the 16 patients in the control group; 4/16 Nd:YAG-treated patients were free of symptoms at 6-month follow up. | High concern |
Zivanovic 2024 [34] | 66 | 59.3 (22–86) | Vulva | Group 1 (44): l dual neodymium:yttrium–alumin-ium–garnet (Nd:YAG)/erbium:yttrium–aluminium–gar-net (Er:YAG) laser at baseline, months 1, 2 and 4 Group 2 (22): topical clobetasol propionate (17 patients used 0.05% oitment and 5 preferred 0.05% cream) first 4 days/week for 8 weeks (phase I) then 4 days/week every 2nd week for 8 weeks (phase II) and finally 4 days/week every 4th week for 8 weeks (phase III) |
Mean change in total LS score and subcategories at 6 months:
Mean change in total VAS score (itching, burning and pain) and subcategories at 6 months:
Mean change in total VSQ score and subcategories at 6 months:
Regarding reported patient satisfaction (PGI-I) for laser vs. steroid groups respectively:
* p < 0.05 considered statistically significant | Pain/discomfort during laser sessions:
Within the first week of laser:
| 6 months total with 2 months follow up | No reported relapses or remissions | Low concern |
Salgado 2023 [35] | 20 | Not reported | Vulva | Fractional CO2 laser (11): three sessions, with the following settings: 25 watts/ Stack 1/ime 700 microseconds/Spacing 700 micromillimeters. Clobetasol propionate ointment 0.05% (9): nightly in the first month, followed by nightly on alternate days in the second month, then nightly on two consecutive days of the same week (Saturdays and Sundays) in the third month, as needed afterwards without exceeding twice weekly | Mean change in WHOQOL-BREF domains after 3 months of treatment:
Regarding self-perceived itch, dysuria, pain/sting, sexual activity, appearance, difficulty and patient satisfaction at 3 months:
At 12 months:
| No reported adverse events | 12 months | No reported relapses or remissions at 12 months, however higher occurrence of mild hyperkeratosis and lichenification and excoriations in laser groups | Low concern |
Terras 2014 [36] | 26 | 60.83 (20–81) | Vulva | Group 1 (13): Clobetasol propionate 0.05% ointment once daily for 3 months (CP) Group 2 (13): Medium-dose ultraviolet A1 (50 J/cm2) home-based phototherapy, performed 4 times weekly for 3 months (UVA) | Change in mean…
| Initial increase in pruritus for UVA-treated patients, treated with petroleum jelly applied within 30 min of radiation to prevent dehydration, which led to marked improvement | 6 months | Three months after end of therapy, all primary and secondary outcomes points returned to baseline levels in all patients, suggesting only transient benefit from these therapies | Some concern |
Shi 2016 [37] | 40 | 51.4 ± 15.6 (range not reported) | Vulva | ALA-PDT (20): 10% 5-aminolevulinic acid photodynamic therapy (ALA-PDT) cream applied to the lesions with a 1-cm margin and incubated for 3 h. The lesions were irradiated with 100 J/cm2 633 nm red light at 100 mW/cm2. The same PDT procedure was repeated 3 times at 2-week intervals. CP (20): Topical 0.05% clobetasol propionate ointment applied by the patient nightly for 8 weeks. | Changes in clinical scores (hyperkeratosis, sclerosis, atrophy, depigmentation) Scores: 0 = absent, 1 = mild, 2 = moderate, 3 = severe Mean changes not reported. Hyperkeratosis:
Atrophy:
Sclerosis:
Depigmentation:
Changes in symptom scores (pruritus, burning and pain feeling)
Mean reduction in lesion size:
Change in ratios of the vulvar surface affected by VLS: Scored as 0 = none, 1 = less than 25%, 2 = 25–50%, 3 = more than 75% of the vulvar surface affected
| ALA-PDT:
CP:
| 6 months | ALA-PDT: 14/20 (70%) complete response 4 (20%) partial response 2 (10%) minimal response Clobetasol propionate: 7/20 (35%) complete response 6 (30%) partial response 7 (35%) minimal response. Rate of complete response in the ALA-PDT group was much higher than that in the CP group (p < 0.05, χ2 = 4.912) Rate of relapse: All patients finished the 6-month follow-up. In ALA-PDT group: 1 out of 14 (7.1%) patients relapsed one month after completion of treatment. The remaining 13 patients showed no signs of recurrence during follow-up. In CP group, 7 out of 7 (100%) patients relapsed one month after treatment. | Some concerns |
Li 2004 [38] | 31 | 38.5 | Vulva | Focused ultrasound therapy
| Response measured based on the reduction of pruritus, changes of the skin elasticity and color, decreased percentage of the involved area, and changes in histological findings Cured: (17/31, 54.84%) Improvement: (12/31, 38.71%) Persistent disease: (2/31, 6.45%) Overall response rate: (29/31, 93.55%) | None | 2 years | 17 patients in remission | Some concerns |
Oral Therapies | |||||||||
Bousema 1994 [39] | 78 | NR (18-83) | Vulva | Experimental group (22): Acitretin 30 mg once daily for 16 weeks, could be reduced to 20 mg once daily in case of adverse reactions after 4 weeks (AC) Control group (24): Placebo (PLA) | Improvement in…
| Cheilitis and xerosis in all AC patients, 1/3 of PLA patients Severe peeling of palms and soles in AC group (11) Increased hair loss higher in AC (23) than PLA (2) | 16 weeks | None | Low concern |
Psychological Counselling | |||||||||
Vittrup 2022 [40] | 158 | Median, IQR Intervention group: 53 (33.2–60.5) Median, IQR Treatment Group: 50.5 (30.8–57.0) | Vulva | Control group: usual management where woman would receive oral instruction at diagnosis, treatment, and consultation with nurse specialized in vulvar diseases to follow-up regarding compliance, adherence and support (80) Usual treatment + psychosexual counselling group offered 8 individual sessions of 45 min of counselling based on individual needs (78) | Female Sexual Function Index-FSFI Scores:
Dermatology Life Quality Index-DLQI Scores:
WHO-5 Wellbeing Index Scores:
Effect size of sexual counselling on sexual activity:
| None | 6 months | Not applicable to this study | Low concern |
# Patients | Mean Age (Age Range) | Affected Region | Treatment Modality | Response | Adverse Events | Follow Up Duration | Remission or Recurrence | Risk of Bias | |
---|---|---|---|---|---|---|---|---|---|
Lindhagen 1996 [41] | 30 | NR | Penis | Group 1 (15): Clobetasol propionate Group 2 (15): Placebo | Clobetasol Propionate: Improvement: n = 10 (+7 from placebo group who were switched) No effect: n = 3 Withdrawal: n = 2 Placebo: Improvement: n = 7 No effect: n = 7 (subsequently given clobetasol propionate and improved) Withdrawal: n = 1 | NR | 6 months | No information about relapse or complete remission provided. | Low concern |
Laino 2013 [42] | 28 | NR (25–65) | Penis | Group 1 (14): Subdermal polydeoxyribonucleotide infiltration, 8 sessions total, in association with nightly clobetasol propionate 0.05% (PDRN) for 4 months Group 2 (14): Clobetasol propionate 0.05% nightly (CP) for 4 months | Change in median value of…
| None | 6 months | PDRN: 14 remission, 0 relapse CP: 8 remission, 6 relapse | Some concerns |
Ioannides 2010 [43] | 51 | For control group: 57.79 (38–75) For treatment group: 56.56 (38–74) | Male genitalia | Treatment (34): systemic acitretin 35 mg daily for 20 weeks Control (17): placebo capsules (identical in size and color to acitretin) for 20 weeks | Two patients, 1 on acitretin and 1 on placebo, withdrew from the study due to disease associated complications (phimosis) which demanded surgical management Mean change in total clinician score (TCS)
Mean change in total quality of life
| Acitretin group:
Control group:
| 36 weeks | Complete response: 36.4% (12 of 33) of the subjects on acitretin and 6.3% (12 of 16) of controls Partial response: 36.4% (12 of 33) of the treatment group and in 12.5% (2 of 16) of the control group. Disease remained stable in: 21.2% (7 of 33) of the acitretin group and 31.3% (5 of 16) of the control groups Disease progression: 6.1% (2 of 33) of individuals on acitretin and 50.0% (8 of 16) on placebo | Low concern |
# Patients | Mean Age (Age Range) | Affected Region | Treatment Modality | Response | Adverse Events | Follow Up Duration | Remission or Relapse | Risk of Bias | |
---|---|---|---|---|---|---|---|---|---|
Tedesco 2020 [44] | 40 (24 M, 16 F) | Entire sample: 43 (18–78) Female patients: 59 (29–78) Male patients:49 (18–76) | Female and male genitalia, not otherwise specified | Group 1 (20 total, 5F and 15M): Intradermal injection of adipose tissue derived-stromal vascular fraction; 2 surgical procedures 4 months apart Group 2 (20 total, 11F and 9M): Intradermal injection of combined purified AD-SVF and platelet rich plasma (PRP); 2 surgical procedures 4 months apart | Mean clinical score at 6 months post-second injection (score ranging from 0 (disease stability) to 3 (great functional improvement with reduction of symptoms until their disappearance) based on subjective itch, pain, burning sensation and dyspareunia on 10 level VAS)
Mean change in QoL (based on DLQI questionnaire)
| None | 6 months | 13 patients had complete resolution of symptoms 23 showed significant improvement in symptoms 4 showed no changes 2 reported a reduction of white lesions | Some concerns |
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Conte, S.; Daraj Mohamed, S.; Shergill, M.; Yacovelli, A.; Johnston, L.; Starkey, S.; Cohen, Y.; Law, A.; Litvinov, I.V.; Mukovozov, I. Treatment Modalities for Genital Lichen Sclerosus: A Systematic Review. Dermato 2024, 4, 136-172. https://doi.org/10.3390/dermato4040014
Conte S, Daraj Mohamed S, Shergill M, Yacovelli A, Johnston L, Starkey S, Cohen Y, Law A, Litvinov IV, Mukovozov I. Treatment Modalities for Genital Lichen Sclerosus: A Systematic Review. Dermato. 2024; 4(4):136-172. https://doi.org/10.3390/dermato4040014
Chicago/Turabian StyleConte, Santina, Sarah Daraj Mohamed, Mahek Shergill, Alexandra Yacovelli, Leah Johnston, Samantha Starkey, Yossi Cohen, Angela Law, Ivan V. Litvinov, and Ilya Mukovozov. 2024. "Treatment Modalities for Genital Lichen Sclerosus: A Systematic Review" Dermato 4, no. 4: 136-172. https://doi.org/10.3390/dermato4040014
APA StyleConte, S., Daraj Mohamed, S., Shergill, M., Yacovelli, A., Johnston, L., Starkey, S., Cohen, Y., Law, A., Litvinov, I. V., & Mukovozov, I. (2024). Treatment Modalities for Genital Lichen Sclerosus: A Systematic Review. Dermato, 4(4), 136-172. https://doi.org/10.3390/dermato4040014