Medicine, Faculty of
Non UBC
Dermatology and Skin Science, Department of
DSpace
Conte, Santina
Daraj Mohamed, Sarah
Shergill, Mahek
Yacovelli, Alexandra
Johnston, Leah
Starkey, Samantha
Cohen, Yossi
Law, Angela
Litvinov, Ivan V.
Mukovozov, Ilya
Background: Lichen sclerosus (LS) is a chronic, inflammatory dermatosis that affects both genital and extragenital sites. It is often difficult to treat and may lead to a variety of complications if not adequately treated. The mainstay of therapy involves topical corticosteroids, topical calcineurin inhibitors, and systemic immunomodulators. Although a variety of topical, oral, and procedural therapies are available, a review comparing relative efficacy is lacking. To this end, this systematic review aimed to summarize the literature regarding treatment modalities and their respective response rates in patients with genital LS. Methods: A literature search was conducted in accordance with PRISMA guidelines. Results: This review qualitatively summarizes information from 31 randomized controlled trials, encapsulating a total of 1507 patients with LS, the majority of which were female (n = 1374, 91%). Topical corticosteroids, the mainstay of therapy for LS, were discussed throughout the literature, and proved to be more efficient than topical calcineurin inhibitors, topical hormonal therapy, topical vitamin E oil and cold cream. However, other treatment modalities proved to be more efficient than topical corticosteroids, including CO₂ and Nd:YAG laser therapies, and the addition of polydeoxyribonucleotide intradermal injections, to steroid therapy. Finally, other modalities that proved to be efficient in the treatment of LS included silk undergarments, human fibroblast lysate cream, platelet-rich plasma, acitretin, and surgical intervention. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials. Limitations included the inclusion of only randomized controlled trials, moderate or high risk of bias, and heterogeneity in treatment regimens, among others. Conclusion: Although high-potency topical corticosteroids have validated efficacy in the management of LS, other treatment modalities, including steroid-sparing agents and/or procedural adjuncts, have been demonstrated to have a beneficial role in the treatment of LS.
Citation: 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 GenitalLichen Sclerosus: A SystematicReview. Dermato 2024, 4, 136–172.https://doi.org/10.3390/dermato4040014Academic Editor: Thilo GambichlerReceived: 4 August 2024Revised: 12 October 2024Accepted: 15 October 2024Published: 19 October 2024Copyright: © 2024 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Systematic ReviewTreatment Modalities for Genital Lichen Sclerosus:A Systematic ReviewSantina Conte 1 , Sarah Daraj Mohamed 1, Mahek Shergill 2 , Alexandra Yacovelli 1, Leah Johnston 3,Samantha Starkey 4 , Yossi Cohen 1, Angela Law 5,6, Ivan V. Litvinov 7 and Ilya Mukovozov 8,*1 Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H4A 3J1, Canada;santina.conte@mail.mcgill.ca (S.C.); sarah.darajmohamed@mail.mcgill.ca (S.D.M.);alexandra.yacovelli@mail.mcgill.ca (A.Y.); yossi.cohen@mail.mcgill.ca (Y.C.)2 Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8P 1H6, Canada;mahek.shergill@medportal.ca3 Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z5, Canada;leah.johnston2@ucalgary.ca4 Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada;samantha.starkey@nemours.org5 Department of Dermatology and Skin Science, University of British Columbia,Vancouver, BC V5Z 4E8, Canada; angela.m.law@gmail.com6 Providence Health Care Dermatology, Mount Saint Joseph Hospital, Vancouver, BC V5T 3N4, Canada7 Division of Dermatology, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada;ivan.litvinov@mcgill.ca8 Toronto Dermatology Centre, Toronto, ON M3H 5Y8, Canada* Correspondence: mukovoi@gmail.com; Tel.: +1-416-633-0001Abstract: Background: Lichen sclerosus (LS) is a chronic, inflammatory dermatosis that affects bothgenital and extragenital sites. It is often difficult to treat and may lead to a variety of complications ifnot adequately treated. The mainstay of therapy involves topical corticosteroids, topical calcineurininhibitors, and systemic immunomodulators. Although a variety of topical, oral, and proceduraltherapies are available, a review comparing relative efficacy is lacking. To this end, this system-atic review aimed to summarize the literature regarding treatment modalities and their respectiveresponse rates in patients with genital LS. Methods: A literature search was conducted in accor-dance with PRISMA guidelines. Results: This review qualitatively summarizes information from31 randomized controlled trials, encapsulating a total of 1507 patients with LS, the majority of whichwere female (n = 1374, 91%). Topical corticosteroids, the mainstay of therapy for LS, were discussedthroughout the literature, and proved to be more efficient than topical calcineurin inhibitors, topicalhormonal therapy, topical vitamin E oil and cold cream. However, other treatment modalities provedto be more efficient than topical corticosteroids, including CO2 and Nd:YAG laser therapies, andthe addition of polydeoxyribonucleotide intradermal injections, to steroid therapy. Finally, othermodalities that proved to be efficient in the treatment of LS included silk undergarments, humanfibroblast lysate cream, platelet-rich plasma, acitretin, and surgical intervention. The risk of biaswas assessed using the Cochrane risk-of-bias tool for randomized trials. Limitations included theinclusion of only randomized controlled trials, moderate or high risk of bias, and heterogeneity intreatment regimens, among others. Conclusion: Although high-potency topical corticosteroids havevalidated efficacy in the management of LS, other treatment modalities, including steroid-sparingagents and/or procedural adjuncts, have been demonstrated to have a beneficial role in the treatmentof LS.Keywords: lichen sclerosus; treatment; management; response; steroids; surgeryDermato 2024, 4, 136–172. https://doi.org/10.3390/dermato4040014 https://www.mdpi.com/journal/dermatoDermato 2024, 4 1371. IntroductionLichen sclerosus (LS) is a chronic inflammatory dermatosis commonly affectinganogenital skin and is often difficult to treat, leading to a multitude of complications [1,2].Most notably, LS has the capacity for malignant transformation, including anogenital squa-mous cell carcinoma and verrucous carcinoma [3,4]. Its exact prevalence is unknown, withthe literature ranging from 1 in 1000 to 1 in 300 patients living with the disease [5]. Suchvariations are hypothesized to be secondary to frequent misdiagnosis and asymptomaticpatients [5]. While both sexes can be affected, the prevalence is thought to be a lot higherin females with upwards of a 10:1 female to male ratio [5]. Moreover, all ages can beaffected, with women typically presenting with a bimodal age distribution with one peakbetween the ages of 8 and 13, and the second being during the fifth and sixth decades [5].It commonly presents with pruritus, pain/discomfort, atrophy and scarring, and has asignificant impact on patients’ quality of life [6,7]. LS affects patients’ quality of life not onlysymptomatically, but also due to its associated loss of normal vaginal or penile architectureresulting in psychological distress [8]. Treatment is difficult, and, in cases where LS is notrecognized early and treated aggressively, it can progress and cause debilitating symptomsand significant morbidity [9]. As with many inflammatory dermatoses, the gold standardtreatment is high-potency topical corticosteroids, and in patients with penile involvement,circumcision is indicated if patients are refractory to corticosteroids [10]. However, recentstudies have begun to explore a multitude of other treatment modalities for LS, includingtopical calcineurin inhibitors, topical and systemic retinoids, and phototherapy [11]. Itis important to note that while a plethora of treatment modalities have been explored inthe literature and may have been proven to be efficacious in managing the symptoms andarchitectural changes associated with LS, only corticosteroids have the capacity to reducethe risk for malignant potential [12]. Moreover, in addition to being useful in avoidingprogression to differentiated vulvar intraepithelial neoplasia (dVIN), topical corticosteroidsare useful in the follow-up of patients with previously surgically excised dVIN to reducethe risk of further invasive malignancy and should thus be recommended to this patientgroup [13]. Ultimately, a systematic review was conducted to summarize the efficiency ofvarious treatment modalities for genital LS.2. MethodsWe conducted a systematic review of the literature adhering to PRISMA reportingguidelines [14].2.1. Search Strategy, Study Eligibility Criteria, and Study SelectionA literature search of the PubMed, MEDLINE, and Embase databases was performedon 23 April 2024 using the following search strategy: “lichen sclerosus” and (“genital” or“vulvar” or “vaginal” or “penile”) and (“treatment” or “management”). All randomizedcontrolled trials (RCTs) reporting treatment modalities and their associated outcomes forlichen sclerosus were included. In vitro, histological and animal studies were excluded.Non-English articles and non-RCT studies were also excluded. Finally, studies that didnot distinguish treatment modalities used by sex were also excluded. Title and abstractscreening was completed by three independent researchers (S.C., S.D.M., and M.S.) usingCovidence online systematic review software (www.covidence.org). Full texts to identifyrelevant studies were assessed by six reviewers. Conflicts were resolved by the primaryauthor (S.C.) and the senior author (I.M.).2.2. Data Extraction and SynthesisThree reviewers (S.C., S.D.M., and M.S.) independently extracted data from eligiblestudies using a standardized extraction form that included title, authors, year of publication,sample size, and key findings divided by sex, including mean age, age range, affectedregion(s), treatment modalities, treatment response, treatment-related adverse events, andfollow-up duration. Three authors (S.C., S.D.M., and M.S.) evaluated the extracted dataDermato 2024, 4 138and synthesized the available evidence in an iterative manner. A pooled analysis wasperformed for studies with available outcome data. A risk of bias analysis was conductedby two different authors for all included studies using the Cochrane risk-of-bias tool forrandomized trials. This systematic review was not registered in a database and a reviewprotocol was not prepared.3. Results3.1. Study and Patient CharacteristicsFollowing the title and abstract screening of 66 studies, and full text screening of33 studies, 31 studies ultimately met inclusion criteria (Figure 1). This pooled analysisreports on 1507 cases of LS, 1374 (91%) of which occurred in females, with available data ontreatment outcomes. The mean age of females included in this review was 56.4 years (range12 to 86), whereas only one of the three male-only studies noted mean age (57.4 years) andone was focused on LS in male children. All 1374 cases of LS presenting in females werenoted to affect the vulva, while 58 male LS cases affected the penis, and 51 cases localizedto the male genitalia, not otherwise specified (Tables 1 and 2).Dermato 2024, 4, FOR PEER REVIEW 3 follow-up duration. Three authors (S.C., S.D.M., and M.S.) evaluated the extracted data and synthesized the available evidence in an iterative manner. A pooled analysis was per-formed for studies with available outcome data. A risk of bias analysis was conducted by two different authors for all included studies using the Cochrane risk-of-bias tool for ran-domized trials. This systematic review was not registered in a database and a review pro-tocol was not prepared. 3. Results3.1. Study and Patient CharacteristicsFollowing the title and abstract screening of 66 studies, and full text screening of 33 studies, 31 studies ultimately met inclusion criteria (Figure 1). This pooled analysis reports on 1507 cases of LS, 1374 (91%) of which occurred in females, with available data on treat-ment outcomes. The mean age of females included in this review was 56.4 years (range 12 to 86), whereas only one of the three ale-only studies noted mean age (57.4 years) and one was focused on LS i male children. All 1374 cases of LS presenting in fem les were noted to affect the vulva, whi 58 male LS cases ff cted the p is, and 51 cases localized to the male genitalia, not otherwise specified (Tables 1 and 2). Figure 1. PRISMA flow diagram of included studies. Figure 1. PRISMA flow diagram of included studies.Dermato 2024, 4 139Table 1. Management of LS in female patients.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasTopical Steroids as a Single ModalityCorazza2016 [15] 48 64.14 (NR) VulvaGroup 1 (24): Clobetasolpropionate 0.05% ointmenttwice weekly for 52 weeks (CP)Group 2 (24): Mometasonefuroate 0.1% ointment twiceweekly for 52 weeks (MF)Mean change in features:• Itching: 0.01 in CP, 0.31 in MF, no statisticaldifference between groups (p = 0.42)• Burning: 0.98 in CP, 0.55 in MF, no statisticaldifference between groups (p = 0.52)• Global Subjective Score: 0.22 in CP, 0.77 in MF,no statistical difference between groups (p = 0.48)• Global Objective Score: −0.27 in CP, −0.5 in MF,no statistical difference between groups (p = 0.14)None 52 weeks3 cases of relapse: 2 inCP, 1 in MFMean time to relapse:30 weeks (range 20–38)SomeconcernVirgili2014 [16] 54 64.2 (NR) VulvaGroup 1 (27): Clobetasolpropionate 0.05% ointmentfive days per week for 4 weeks,then on alternate days for4 weeks, then twice weekly for4 weeks (CP)Group 2 (27): Mometasonefuroate 0.1% ointment fivedays per week for 4 weeks,then on alternate days for4 weeks, then twice weekly for4 weeks (MF)CP:• Responders (significant improvement in clinicalpicture and symptoms): 24 (88.9%)• Non-responders: 1 (3.7%)• >75% improvement in Global Subjective Score:16 (59.3%)• >50% improvement in Global Subjective Score:21 (77.8%)• >75% improvement in Global Objective Score:10 (37.0%)• >50% improvement in Global Objective Score:21 (77.8%)MF:• Responders: 24 (88.9%)• Non-responders 2 (7.4%)• >75% improvement in Global Subjective Score:18 (66.7%)• >50% improvement in Global Subjective Score:21 (77.8%)• >75% improvement in Global Objective Score:13 (48.2%)• >50% improvement in Global Objective Score:22 (81.5%)None 12 weeks24 patients responded,while 1 did not for CP24 patients responded,while 2 did not for MFSomeconcernDermato 2024, 4 140Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasBorghi2015 [17] 64 60.95 (NR) VulvaGroup A (32): Mometasonefuroate 0.1% ointment dailyfor 5 days per week for4 weeks, then on alternatedays for 4 weeks, then twiceweekly for 4 weeksGroup B (32): Mometasonefuroate 0.1% ointment 5 daysweekly• 27 patients (84%) in Group A experienced clinicalresolution• 25 patients (78%) in Group B considered asresponders• Difference in response between the two groupswas not statistically significant• Relative risk of non-response Group A:Group B =0.94 (CI 0.26–3.40)Change in mean. . .• Itching: 5.45 in Group A (p < 0.001), 5.29 in GroupB (p < 0.001), no statistical difference betweengroups (p = 0.15)• Burning: 4.11 in Group A (p < 0.001), 3.28 in GroupB (p < 0.001), no statistical difference betweengroups (p = 0.41)• Global Subjective Score: 9.43 in Group A(p < 0.001), 8.79 in Group B (p = 0.002), nostatistical difference between groups (p = 0.26)• Global Objective Score: 3.95 in Group A (p < 0.001),2.61 in Group B (p < 0.001), no statistical differencebetween groups (p = 0.22)None 12 weeks27 responders and4 non-responders inMF125 responders and4 non-responders inMF2SomeconcernVirgili2013 [18] 27 60.53 (NR) VulvaTreatment Phase (12 weeks):• Mometasone furoate0.1% ointment oncedailyMaintenance Phase (52 weeks),whereby all patients wereassigned to one modality:• Mometasone furoate(MF) 0.1% ointmenttwice weekly (8)• Topical vitamin E oil(VitE) once daily (9)• Cold cream (CC) oncedaily (8)Treatment Phase (27 patients):• 25/27 completely or almost completely healed onboth objective and subjective protocol-definedscores• 1 patient dropped out, 1 patient discovered shewas pregnant• Mean objective signs score (MOS): MF 8.5 → 0.0,VitE 6.75 → 0.0, CC 6.75 → 1.25• Mean itching score (MIS): MF 5.75 → 0.0, VitE 8.0→ 0.0, CC 5.75 → 1.25• Mean burning score (MBS): MF 6.75 → 2.0, VitE4.75 → 1.0, CC 5.0 → 1.75Maintenance Phase (25 patients):• MF (7): 0 relapses, MOS 0.0 → 0.2, MIS 0.0 → 1.0,MBS 2.0 → 1.75• VitE (9): 5 relapses, MOS 0.0 → 1.5, MIS 0.0 → 0.5,MBS 1.0 → 0.5• CC (8): 5 relapses, MOS 1.25 → 1.0,MIS 1.25 → 0.0, MBS 1.75 → 0.75None 64 weeksMF: 7 remission,0 relapseVitE: 4 remission,5 relapseCC: 3 remission,5 relapseMedian time to relapsefor VitE and CC: 21.6weeksSomeconcernDermato 2024, 4 141Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasTopical Corticosteroids and Adjunct TherapiesD’Antuono2011 [19] 42 51.5 (22–79) VulvaTreatment Phase (6 months):• Clobetasol propionate0.05% ointment oncenightly• Standard moisturizercontaining vitamin Eonce daily• White cotton (CT) (21)or Dermasilk fabric (DS)briefs (21)CT Group:• Symptoms: Complete response (CR) = 0,good/partial response = 17, poor response = 4• Clinical signs: CR = 0, GR = 12, PR = 9DS Group:• Symptoms: CR = 1, GR = 20, PR = 0• Clinical signs: CR = 2, GR = 19, PR 03 cases of Candidavulvovaginitis in CT group 6 monthsCT: Remission in 0patients, relapse notnotedDS: Remission in 2patients, relapse notnotedSomeconcernNon-Steroid TopicalsCattaneo1996 [14] 32 60 (28–85) VulvaFirst part of treatment (32):• Clobetasol propionate0.5% cream twice dailyfor 4 weeks, once a dayfor 8 weeks and thentwice a week for 12weeks (both groups)Second part of treatment:• Experimental group(16): 2% topicaltestosterone propionatein a petrolatum-vehiclegalenic preparation oncedaily for 24 weeks (TP)• Control group (16):Petrolatum vehicleplacebo once daily for24 weeks (PLA)First part of treatment:• Symptomatic relief by all patients, reduction incumulative score for symptoms from 58 to 9(p < 0.001)• Reduction in cumulative score for gross aspectsfrom 82 to 38 (p < 0.001)• Evident reduction in hyperkeratosis and sclerosus• Very little change in atrophy• Total disappearance in erosion and purpura• Complete regression of histological changes in12 patients, with remaining patients showing someimprovement; marked improvement ininflammatory infiltrate, edema and fibrosisSecond part of treatment:• Cumulative score showed a statistically significantworsening with TP (6 to 23, p < 0.05)• Further improvements in symptoms in 3 PLApatients, recurrence of itching to a mild degree in 3other PLA patients (score change insignificant)• Better response to PLA than TP for symptoms(p < 0.01), no difference for gross aspects(non-significant)Burning (4) and itching (9)on application oftestosterone ointment48 weeksSymptomatic relief inall patients in firstphaseWorsening ofsymptoms in patientsin TP arm of study3 patients maintainedon placebo improvedLowconcernDermato 2024, 4 142Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasFunaro2014 [20] 55 46.6 (NR) VulvaGroup 1 (28): Tacrolimus 0.1%ointment daily for 3 months(CL)Control group (27): Clobetasolpropionate 0.05% ointmentdaily for 3 months (CP)• Change in pruritus: 2.0 in TL, 3.5 in CP• Change in burning/pain: 1.75 in TL, 2.5 in CP• Significant decrease in pruritus and burning/painfor all participants (p < 0.001)• Change in pruritus (p = 0.108) and burning(p = 0.172) not statistically different between thetwo groups, but CP more effective in reducingburning/pain and pruritus after 1 month than TL,but CP more effective in reducing burning/painand pruritus after 1 month than TL• More significant decrease in papules and atrophicpatches than TL (perineal 0 = 0.036, clitoralp = 0.001)• At end of study: 19 TL patients versus 9 CPpatients still had some clinical signs of LS(p = 0.015)• Number of participants with no clinical signs orreported symptoms significantly higher in CP (15)than the TL (4) groupNone 3 monthsRemission in 9/28(32%) of CP patients,only 19/27 (70%) of TLpatientsLowconcernGoldstein2011 [21] 38 NR (NR) VulvaGroup 1 (17): Pimecrolimus 1%cream twice daily for 12 weeks(PIM)Group 2 (19): Clobetasolpropionate 0.05% cream twicedaily for 12 weeks (CP)• Histopathological improvement in inflammationsignificant for both groups: p = 0.001 for CP,p = 0.008 for PIM, CP superior to PIM (p = 0.015)• More non-responders in PIM than CP group:8 PIM, 1 CP• Mean change in pruritus: CP 4.5, PIM 3.5,difference not statistically significant (p = 0.319)• Mean change in burning and pain: CP 3.7, PIM 3.8,difference not statistically significant (p = 0.932)• Both CP and PIM were effective in decreasingInvestigator Global Assessment scores (p = 0.001)and its 3 subscales (severity of disease [p = 0.001],lichenification [p = 0.001], ulceration [p = 0.25])None 12 weeks26 patients completedthe follow-up period,where 24 showedimprovement and11 (42%) experiencedremission (not brokendown by treatmentarm)LowconcernSideri1994 [22] 58 56.5 (35–83) VulvaGroup 1 (30): 2% Testosteronepropionate in VaselineGroup 2 (28): PetroleumointmentSymptom improvement (pruritus vulvae, burning):Testosterone propionate group:• Improved (66.6%, n = 20)• Unchanged (20%, n = 6)• Worsened (13.4%, n = 4)Placebo:• Improved (75%, n = 21)• Unchanged (17.8%, n = 5)• Worsened (7.1%, n = 2)No significant difference found between groups.n = 4, adverse events notspecified 12 monthsImprovement indystrophy in17 patients (group notspecified), but nohistologicaldemonstration ofregression in any of thecases.LowconcernDermato 2024, 4 143Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasGunthert2022 [23] 37 34.52 (NR) VulvaGroup 1 (17): Progesterone 8%ointment, 2 g daily for 12weeks (PRO)Group 2 (20): Clobetasolpropionate 0.05% ointment, 2 gdaily for 12 weeks (CP)Change in:• Clinical severity: 0.1 in PRO, 1.7 in CP, difference1.61 (p = 0.0009)• Symptom severity: 1.4 in PRO, 2.8 in CP,difference 1.32 (p = 0.095)• Short Form-12 physical component score: 0.1 inPRO, −0.4 in CP, difference −0.30 (p = 0.151)Short Form-12 mental component score: −0.2 in PRO,0.3 in CP, difference 0.41 (p = 0.169)CP: Genital herpes (2),mycotic genital infection (1),urinary tract infection (2)PRO: Mycotic genitalinfection (1), vulvitis (2),urinary tract infection (1),peritonitis (1)24 weeksRemission in 6/10 PROpatients, 13/16 CPpatientsLowconcernBracco1993 [24] 79 57 (27–83) VulvaGroup 1 (20): Clobetasolpropionate 0.05% topicalGroup 2 (20): Testosterone 2%topicalGroup 3 (20): Progesterone 2%topicalGroup 4 (19): Cream-basedpreparation topicalSymptoms (itching, burning, pain and dyspareunia)were classified from 0–3, with 3 most severe.Symptom improvement:Clobetasol propionate: 15%Testosterone: 40%Progesterone: 40%Cream-based preparation: 21%.Symptom unchanged:Clobetasol propionate: 10%Testosterone: 40%Progesterone: 50%Cream-based preparation: 69%Gross changes: Significant difference in clobetasol grouponly (p < 0.001, CI 2.93–4.97)Gross appearance mean score, clobetasol: 5.8 to 1.9Histological evaluation: Significant difference inclobetasol group only (p < 0.001, CI 2.29–4.65), meanscore 7.1 to 3.7None 3 monthsSymptom remission (nosymptoms and/orlesions remaining):Clobetasol propionate:75%Testosterone: 20%Progesterone: 10%Cream-basedpreparation: 10.5%.Follow up encouragedfor an additional3 months for clobetasolgroup, in whichpatients encouraged touse it twice weekly for3 more months. Ofremaining 13 patients,11 continued goodresponse to therapy, 2who discontinued hadrecurrence.LowconcernDermato 2024, 4 144Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasGoldstein2015 [25] 30 58 (NR) VulvaTreatment Group (TG) (15):Human fibroblast lysate creamtwice daily for 12 weeksControl Group (CG) (15):Placebo cream with the sameemollient base as the treatmentcream twice daily for 12 weeks• Significant improvement of Investigator GlobalAssessment (IGA) score at 12 weeks for bothgroups; 60% of TG showed a decrease of 1+ points,while only 33% of CG patients had improvement• Mean decrease in IGA points: TG 0.9, CG 0.5,p > 0.2• Improvement in pruritus: TG 43% (p = 0.005), CG51% (p = 0.001), p = 0.226• Improvement in pain and burning: TG 51%(p = 0.002), CG 43% (p = 0.005), p = 0.86• No significant difference in sexual function foreither group: TG p = 0.98, CG p = 0.89No significant change in histopathologic inflammationfor both groupsNone 12 weeks No relapse noted SomeconcernVirgili2013 [26] 8061.85(12.17–84.92) VulvaMaintenance therapy(following a 12-week activetreatment phase on topical0.1% mometasone furoateointment daily; patients whoachieved a symptomatologicVAS global score ≤ 5/30 andan IGA score ≤ 2 (total oralmost total healing) werejudged as “treatmentresponsive” and were eligiblefor the MP) with:• Topical vitamin E oil for52 weeks (44)• Emollient (cold cream)for 52 weeks (36)Primary efficacy point: relapse rate at both week 26 and52Second efficacy variable: mean time to relapse, definedas number of weeks from start of maintenance phase(MP) until LS relapseTotal 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 maintenancetreatment:• Vitamin E: cumulative rate 27.8% (10/36),cumulative modified rate 55.6% (10/18)• Emollient: cumulative rate 22.7% (10/44),cumulative modified rate 50.0% (10/20)• Differences not statistically significantMedian time to relapse:• Vitamin E: 20 weeks• Emollient: 18.7 weeks• Not statistically significant (p = 0.7).No observed adverse events 52 weeksRelapses• Vitamin E: n = 6at 26 weeks, andan additionaln = 4 at 52 weeks• Emollient: n = 7at 26 weeks, andan additionaln = 3 at 52 weeksDropouts (total n = 42):• Vitamin E: n = 16prior to26 weeks, and anadditional n = 2prior to 52 weeks• Emollient: n = 18prior to26 weeks, and anadditional n = 6prior to 52 weeksLowconcernDermato 2024, 4 145Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasIntradermal InjectionsGutierrez-Ontalvilla2022 [27]19 55.17 (NR) VulvaTreatment Group (TG) (9):24 mL of nanofat mixed withPRP, 2 infiltrations 3 monthsapartControl Group (CG) (10):Topical clobetasol propionate0.05% cream once or twiceweeklyMean change in feature, standard deviation withinbrackets:• Gross elasticity: −0.01 (0.16) in TG, 0.01 (0.23) inCG, p = 0.427• Net elasticity: 0.05 (0.17) in TG, 0.08 (0.26) in CG,p = 0.860• Itching: −2.0 (2.7) in TG, −0.2 (2.3) in CG,p = 0.035• Pain: −4.0 (3.5) in TG, 1.3 (3.5) in CG, p = 0.077• Burning: −3.8 (2.9) in TG, −0.7 (5.7) in CG,p = 0.004• Dyspareunia: −2.0 (4.0) in TG, −0.5 (4.3) in CG,p = 0.022• Global Subjective Score: −11.8 (9.6) in TG, −0.1(9.9) in CG, p = 0.013• Cervical erosions: −0.7 (1.1) in TG, 0.1 (0.7) in CG,p = 0.004• Hyperkeratosis: −0.1 (0.3) in TG, 0.0 (0.0) in CG,p = 0.542• Cracks or fissures: −0.1 (0.3) in TG, 0.0 (0.0) in CG,p = 0.017• Agglutination: −0.2 (0.4) in TG, −0.1 (0.3) in CG,p = 0.075• Introitus stenosis: −0.6 (0.5) in TG, 0.0 (0.0) in CG,p = 0.043• Atrophy: −0.1 (0.3) in TG, −0.1 (0.3) in CG,p = 0.081• Pallor: −1.1 (0.6) in TG, 0.2 (0.6) in CG, p < 0.001• Global Objective Score: −1.1 (0.6) in TG, 0.2 (0.6)in CG, p < 0.001• T lymphocytes: −1.1 (0.3) in TG *, 0.1 (0.8) in CG• Melanophages: −1.3 (1.5) in TG *, 0.2 (0.6) in CG• Eosinophils: −2.9 (1.6) in TG *, 1.6 (−0.3) in CG *• Mast cells: −7.0 (6.1) in TG *, −1.9 (22.8) in CGNone 12 months3 cases of relapse, allpatients in controlgroupSomeconcernDermato 2024, 4 146Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasGoldstein2019 [28] 30 52.6 (NR) VulvaGroup 1 (20): Platelet-richplasma intradermal injections,separated by 6 weeks (PRP)Group 2 (10): Placebo salineinjections (PLA)Change in histopathologic inflammation:• PRP: 5 patients had improvement, 10 had nochange, and 4 had more inflammation• PLA: 5 patients had improvement, 4 had nochange, and 1 had more inflammation• p = 0.542Change in Clinical Scoring System for Vulvar LS: −7.74in PRP, −9.44 in PLA, p = 0.654Bruising 12 weeks Not specified LowconcernEnergy-Based DevicesGuo 2022[29] 50 NR (NR) VulvaExperimental group: CO2 laseronce monthly for 3 months(CO2)Control group 1:Radiofrequency treatmentwith 5-aminolevulinic acid as aphotosensitizer once weeklyfor 10 weeks (RF)Control group 2: Clobetasolpropionate 0.05% ointmentwith traditional Chinesemedicine soaking and washingfor 3–4 months, then onceevery other day for 4 weeks,then twice weekly for 4 weeks(CP)Change in scores at 1 month after treatment:• Pruritus degree: 0.26 in CO2, 0.33 in RF, 0.25 in CP(p = 0.865)• Skin elasticity: 0.57 in CO2, 1.00 in RF, 0.75 in CP(p = 0.122)• Skin color: 1.13 in CO2, 1.33 in RF, 1.75 in CP(p = 0.025)• Lesion scope: 1.61 in CO2, 4.13 in RF, 4.42 in CP(p = 0.097)• Total score: 3.57 in CO2, 4.13 in RF, 4.42 in CP(p = 0.097)Change in scores at 3 months after treatment:• Pruritus degree: 0.17 in CO2, 0.33 in RF, 1.50 in CP(p = 0.057)• Skin elasticity: 0.57 in CO2, 0.93 in RF, 1.08 in CP(p = 0.002)• Skin color: 1.09 in CO2, 1.33 in RF, 1.83 in CP(p = 0.003)• Lesion scope: 1.30 in CO2, 1.47 in RF, 1.75 in CP(p = 0.095)Total score: 3.13 in CO2, 4.07 in RF, 5.58 in CP (p = 0.000)None reported 3 months Not specified SomeconcernDermato 2024, 4 147Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasBurkett2021 [30] 52 64.5 (NR) VulvaGroup 1 (19): FractionatedCO2 laser therapy, 5 courses4–6 weeks apart (CO2)Group 2 (18): Clobetasolpropionate 0.05% ointmentnightly for 1 month, then threetimes weekly for 2 months,then as needed (CP)Change in. . .• Skindex-29 score: −16.83 in CO2, −5.92 in CP,treatment effect of 10.91 (p = 0.007)• Itching: −3.26 in CO2, −1.83 in CP, treatmenteffect of 1.43 (p = 0.136)• Burning: −2.78 in CO2, −1.00 in CP, treatmenteffect of 1.78 (p = 0.081)• Irritation or tearing: −4.15 in CO2, −1.32 in CP,treatment effect of 2.79 (p = 0.009)• Dyspareunia: −0.69 in CO2, −0.14 in CP,treatment effect of 0.55 (p = 0.535)• White plaque: −1.81 in CO2, −1.30 in CP,treatment effect of 0.51 (p = 0.341)• Cigarette paper: −2.58 in CO2, −1.50 in CP,treatment effect of 1.08 (p = 0.058)• Introital narrowing: −1.73 in CO2, −0.70 in CP,treatment effect of 0.18 (p = 0.160)• Loss of labia minora: −0.96 in CO2, −0.78 in CP,treatment effect of 1.50 (p = 0.792)• Fusion of labia minora: −0.50 in CO2, 0.35 in CP,treatment effect of 0.34 (p = 0.279)• Phimosis: −1.28 in CO2, 0.22 in CP, treatmenteffect of 1.5 (p = 0.022)• Fissure: −2.12 in CO2, −1.78 in CP, treatmenteffect of 0.34 (p = 0.634)• Erosion: −2.08 in CO2, −0.57 in CP, treatmenteffect of 1.51 (p = 0.036)• Vulvovaginal Symptom Questionnaire: −3.92 inCO2, −0.58 in CP, treatment effect of 3.34 (p =0.014)• Vaginal Health Index: 1.92 in CO2, −0.43 in CP,treatment effect of −2.35 (p = 0.046)• Patient Global Impression of Improvement: 23 inCO2, 13 in CP, treatment effect of 4.72 (p = 0.073)Patient Global Impression of Satisfaction: 21 in CO2, 9 inCP, treatment effect of 6.07 (p = 0.011)Minor burning andblistering with CO2 (1);reactivation of genitalherpes 1 week after startingCP (1)6 months Not specified SomeconcernMitchell2021 [31] 37 59 (51–64) VulvaGroup 1 (19): FractionatedCO2 laser therapy, 5 courses in24 weeks (CO2)Group 2 (18): Placebo laser(PLA)Change in. . .• Histopathology scale on biopsy: −0.2 in CO2(p = 0.74), 0.1 in PLA (p = 0.91), no statisticaldifference between groups (p = 0.76)• Patients’ Clinical Scoring System for Vulvar LS:−7.1 in CO2 (p = 0.02), −4.8 in PLA (p = 0.04), nostatistical difference between groups (p = 0.60)Providers’ Clinical Scoring System for Vulvar LS: 0.7 inCO2 (p = 0.36), −0.3 in PLA (p = 0.70), no statisticaldifference between groups (p = 0.36)Transient, mild discomfort(n not specified) 24 weeks No remission achievedLowconcernDermato 2024, 4 148Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasKrause2023 [32] 67Low dosegroup: 53(21–80)Normal dosegroup: 52(20–79)VulvaMicroablative CO2 laser lowdose group (LDG) (29): threelaser applications in threesubsequent sessions of threeweeks.Microablative CO2 lasernormal dose group (NDG)(34): three laser applications inthree subsequent sessions ofthree weeks.Mean change in total VAS score at 18 weeks• LDG: − 2.7 (±2.8) (p < 0.0001)• NDG: − 2.4 (±2.3) (p < 0.0001)The difference in mean VAS scores between two groupswas not significant at 18 weeks (p = 0.6244)Mean change in total LS score at 18 weeks:• LDG: −3.3 (p < 0.0001)• NDG: −3.4 (p < 0.0001)The difference in total LS scores between two groups wasnot significant at 18 weeks (p = 0.88)Regarding sexual activity:• LDG: pre-treatment: 13 were sexually active,11 were not sexually active due to LS, 5 were notsexually active due to other reasons;post-treatment: 16 were sexually active, 7 were notsexually active due to LS and 6 for other reasons.• NDG: pre-treatment: 18 were sexually active,10 were not sexually active due to LS, 6 were notsexually active due to other reasons;post-treatment: 23 were sexually active, 5 were notsexually active due to LS and 6 for other reasons.The improvement in sexual activity is not significantlydifferent between two groups at 18 weeks (p = 0.61)Regarding quality of life (QoL):• LDG: pre-treatment: 15 reported severe limitationsand 13 indicated intermittent restrictions;post-treatment: 1 had no more restrictions,7 patients reported severe and 20 intermittentrestrictions. There was an improvement in8 patients (53%).• NDG: pre-treatment: 17 reported severe and14 intermittent limitations; post-treatment:7 reported severe and 24 intermittent restrictions.There was an improvement in 10 patients (58%).• The difference between the number of patientsshowing an improvement in QoL for NDG vs.LDG was not significant (p = 0.80).Burning sensation duringlaser application,not requiring intervention:31No other adverse events orside effects reported.18 weeks No reported relapses orremissions.LowconcernDermato 2024, 4 149Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasBizjakOgrinc2019 [33]40 58 (NR) VulvaExperimental group (20):3 neodymium-doped yttriumaluminium garnet (Nd:YAG)laser treatments every 14 days(Nd:YAG)Control group (20): Topicalbetamethasone twice daily for2 weeks, then once daily forone week, then every secondday for one week (BM)Change in scores at 3 months after treatment:• Burning: 5.0 in Nd:YAG (p < 0.001), 3.6 in BM(p = 0.002), 3.3 in Nd:YAG vs. BM (p = 0.001)• Itching: 6.4 in Nd:YAG (p < 0.001), 3.4 in BM(p = 0.001), 4.1 in Nd:YAG vs. BM (p < 0.001)• Pain: 6.1 in Nd:YAG (p < 0.001), 2.2 in BM(p = 0.037), 3.3 in Nd:YAG vs. BM (p = 0.001)• Total score: 17.5 in Nd:YAG (p < 0.001), 9.1 in BM(p < 0.001), 10.2 in Nd:YAG vs. BM (p < 0.001)Change in scores at 6 months after treatment:• Burning: 4.4 in Nd:YAG (p < 0.001), 1.7 in BM(p = 0.038), 3.9 in Nd:YAG vs. BM (p = 0.008)• Itching: 4.9 in Nd:YAG (p = 0.001), 3.0 in BM(p = 0.095), 3.5 in Nd:YAG vs. BM (p = 0.066)• Pain: 5.4 in Nd:YAG (p < 0.001), 2.0 in BM(p = 0.225), 0.6 in Nd:YAG vs. BM (p = 0.793)• Total score: 14.7 in Nd:YAG (p < 0.001), 5.7 in BM(p = 0.042), 7.6 in Nd:YAG vs. BM (p = 0.080)None 6 months8/20 Nd:YAG-treatedpatients were free ofsymptoms at 3-monthfollow up, comparedwith none of the 16patients in the controlgroup;4/16 Nd:YAG-treatedpatients were free ofsymptoms at 6-monthfollow up.HighconcernDermato 2024, 4 150Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasZivanovic2024 [34] 66 59.3 (22–86) VulvaGroup 1 (44): l dualneodymium:yttrium–alumin-ium–garnet(Nd:YAG)/erbium:yttrium–aluminium–gar-net (Er:YAG)laser at baseline, months 1, 2and 4Group 2 (22): topicalclobetasol propionate (17patients used 0.05% oitmentand 5 preferred 0.05% cream)first 4 days/week for 8 weeks(phase I) then 4 days/weekevery 2nd week for 8 weeks(phase II) and finally 4days/week every 4th week for8 weeks (phase III)• In Group 1: 3 did not complete allocatedintervention (2 became pregnant and 1 could notcome due to COVID-19)• In group 2: 1 did not complete allocatedintervention (did not want to participate anymore)• No patients were lost to FU or had discontinuedintervention at 6 month FUMean change in total LS score and subcategories at 6months:• Group 1: −2.34 ±1.20 (95% CI −2.71 to −1.98,p < 0.001) with significant improvement in erosion(p = 0.011), hyperkeratosis (p < 0.001), fissures(p = 0.005) and atrophy (p < 0.001). Architecturalchanges such as agglutination (p = 0.197) andstenosis (p = 0.467) were not improved by lasertherapy.• Group 2: −0.95 ± 0.90 (95% CI −1.35 to −0.56,p = 0.014) with significant improvement in erosion(p = 0.003), hyperkeratosis (p = 0.035) and fissures(p = 0.046). Changes in agglutination (p = 1.0) andstenosis (p = 1.0) were not significant. Atrophy didnot change as opposed to the laser group.• Total LS score and atrophy at 6 months were bothsignificantly different between two groups(p < 0.001)Pain/discomfort duringlaser sessions:• 5 reported pain inlaser session 1, 3 insession 2, 5 in session3 and 4 in session 4.• No local anaestheticwas necessary.Topical anestheticswere needed in 4.5%(8/176) of alltreatments (never inin session 1, once insession 2, thrice insession 3, and fourtimes in session 4).Within the first week oflaser:• Urinary tractinfection (1)• Vulvar itching (2)Vulvar pain (1)6 monthstotal with 2monthsfollow upNo reported relapses orremissionsLowconcernDermato 2024, 4 151Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasZivanovic2024 [34] 66 59.3 (22–86) VulvaGroup 1 (44): l dualneodymium:yttrium–alumin-ium–garnet(Nd:YAG)/erbium:yttrium–aluminium–gar-net (Er:YAG)laser at baseline, months 1, 2and 4Group 2 (22): topicalclobetasol propionate (17patients used 0.05% oitmentand 5 preferred 0.05% cream)first 4 days/week for 8 weeks(phase I) then 4 days/weekevery 2nd week for 8 weeks(phase II) and finally 4days/week every 4th week for8 weeks (phase III)Mean change in total VAS score (itching, burning andpain) and subcategories at 6 months:• Group 1: total VAS −5.84 ± 6.19 (p < 0.001) withsignificant improvement in: itching −2.89 ± 2.56(p < 0.001), burning −1.91 ± 2.86 (p < 0.001).Changes in unprokoved vulvar pain −1.05 ± 2.48(p = 0.052) and pain at intercourse −1.74 ± 2.36(p = 0.053) were not significant *.• Group 2: total VAS −5.36 ± 6.33 (p = 0.001) withsignificant improvement in: itching −2.36 ± 3.36(p = 0.008) and burning −2.23 ± 3.39 (p = 0.012).• Total VAS scores did not differ significantlybetween two groups (p = 0.881). Changes inunprokoved vulvar pain −0.77 ± 1.95 (p = 0.253)and pain at intercourse −1.78 ± 1.39 (p = 0.088)were not significant *.Mean change in total VSQ score and subcategories at 6months:• Group 1: total VSQ −3.23 ± 3.21 (p < 0.001) withsignificant improvement in: symptoms−1.91 ± 2.37 (p < 0.001) and emotions−0.86 ± 1.41 (p = 0.011). Changes in life impact(−0.45 ± 1.02, p = 0.176) and intercourse(−0.44 ± 1.05, p = 0.275) were not significant.• Group 2: total VSQ −2.32 ± 3.43 (p = 0.043) withsignificant changes in symptoms only−1.23 ± 1.69 (p = 0.010). Changes in emotions(−0.68 ± 1.55, p = 0.180), life impact (−0.41 ± 1.59,p = 0.229) and intercourse (−0.56 ± 0.73, p = 0.320)were not significant.• Changes in total VSQ scores and in subcategorieswere not significant between two groups.Pain/discomfort duringlaser sessions:• 5 reported pain inlaser session 1, 3 insession 2, 5 in session3 and 4 in session 4.• No local anaestheticwas necessary.Topical anestheticswere needed in 4.5%(8/176) of alltreatments (never inin session 1, once insession 2, thrice insession 3, and fourtimes in session 4).Within the first week oflaser:• Urinary tractinfection (1)• Vulvar itching (2)Vulvar pain (1)6 monthstotal with2 monthsfollow upNo reported relapses orremissionsLowconcernDermato 2024, 4 152Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasZivanovic2024 [34] 66 59.3 (22–86) VulvaGroup 1 (44): l dualneodymium:yttrium–alumin-ium–garnet(Nd:YAG)/erbium:yttrium–aluminium–gar-net (Er:YAG)laser at baseline, months 1, 2and 4Group 2 (22): topicalclobetasol propionate (17patients used 0.05% oitmentand 5 preferred 0.05% cream)first 4 days/week for 8 weeks(phase I) then 4 days/weekevery 2nd week for 8 weeks(phase II) and finally 4days/week every 4th week for8 weeks (phase III)Regarding reported patient satisfaction (PGI-I) for laservs. steroid groups respectively:• Very much better: 32% (14/44) vs. 4.5% (1/22)• Much better: 32% (14/44) vs. 41% (9/22)• A little better: 27% (12/44) vs. 36% (8/22)• No change or worsening: 9.0% (4/44) vs. 18.5%(4/22)• The differences for those experiencing no changeor worsening is significant between both groups(p = 0.035).* p < 0.05 considered statistically significantPain/discomfort duringlaser sessions:• 5 reported pain inlaser session 1, 3 insession 2, 5 in session3 and 4 in session 4.• No local anaestheticwas necessary.Topical anestheticswere needed in 4.5%(8/176) of alltreatments (never inin session 1, once insession 2, thrice insession 3, and fourtimes in session 4).Within the first week oflaser:• Urinary tractinfection (1)• Vulvar itching (2)Vulvar pain (1)6 monthstotal with2 monthsfollow upNo reported relapses orremissionsLowconcernDermato 2024, 4 153Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasSalgado2023 [35] 20 Not reported VulvaFractional CO2 laser (11): threesessions, with the followingsettings: 25 watts/ Stack1/ime 700microseconds/Spacing 700micromillimeters.Clobetasol propionateointment 0.05% (9): nightly inthe first month, followed bynightly on alternate days inthe second month, then nightlyon two consecutive days of thesame week (Saturdays andSundays) in the third month,as needed afterwards withoutexceeding twice weeklyMean change in WHOQOL-BREF domains after 3months of treatment:• No statistically significant differences between thetreatment groups, except for the social domain infavor of treatment with clobetasol (3.26 SD 0.88pretreatment; 2.92 SD 0.70, p < 0.05 forclobetasol vs. 3.12 SD 0.95→ 2.88 SD 0.40 for laser)Regarding self-perceived itch, dysuria, pain/sting,sexual activity, appearance, difficulty and patientsatisfaction at 3 months:• Higher degree of satisfaction in laser group interms of self-perception (p = 0.006), but notmaintained at 12 monthsAt 12 months:• Higher occurrence of mild cases of hyperkeratosisand lichenifcation (p = 0.02), in addition toexcoriation (p < 0.03) in the laser group.WHOQOL-BREF domains did not differ between thegroupsNo reported adverse events 12 monthsNo reported relapses orremissions at12 months, howeverhigher occurrence ofmild hyperkeratosisand lichenification andexcoriations in lasergroupsLowconcernTerras2014 [36] 26 60.83 (20–81) VulvaGroup 1 (13): Clobetasolpropionate 0.05% ointmentonce daily for 3 months (CP)Group 2 (13): Medium-doseultraviolet A1 (50 J/cm2)home-based phototherapy,performed 4 times weekly for3 months (UVA)Change in mean. . .• Total Clinician’s Score: 5.0 in CP (p < 0.001), 4.5 inUVA (p = 0.006), no statistical difference betweengroups (p > 0.05)• Itching: 4.6 in CP (p = 0.005), 2.1 in UVA (p = 0.16),statistical difference between groups (p < 0.05)• Burning and/or pain: 4.2 in CP (p = 0.001), 3.2 inUVA (p = 0.01), statistical difference betweengroups (p < 0.05)• Skindex-29 Score: 29.6 in CP (p = 0.009), 4.9 inUVA (p > 0.99), statistical difference betweengroups (p < 0.05)• Histological infiltrate: 0.9 in CP (p = 0.02), 0.2 inUVA (p = 0.51), statistical difference betweengroups (p < 0.05)• Corium thickness on 20-MHx sonography: −786in CP (p = 0.003), −282 in UVA (p = 0.41),statistical difference between groups (p < 0.05)• Dermal density on 20-MHx sonography: 15.0 inCP (p < 0.001), −0.1 in UVA (p = 0.97), statisticaldifference between groups (p < 0.05)Initial increase in pruritusfor UVA-treated patients,treated with petroleum jellyapplied within 30 min ofradiation to preventdehydration, which led tomarked improvement6 monthsThree months after endof therapy, all primaryand secondaryoutcomes pointsreturned to baselinelevels in all patients,suggesting onlytransient benefit fromthese therapiesSomeconcernDermato 2024, 4 154Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasShi2016 [37] 4051.4 ± 15.6(range notreported)VulvaALA-PDT (20): 10%5-aminolevulinic acidphotodynamic therapy(ALA-PDT) cream applied tothe lesions with a 1-cm marginand incubated for 3 h. Thelesions were irradiated with100 J/cm2 633 nm red light at100 mW/cm2. The same PDTprocedure was repeated3 times at 2-week intervals.CP (20): Topical 0.05%clobetasol propionateointment applied by thepatient nightly for 8 weeks.Changes in clinical scores (hyperkeratosis, sclerosis,atrophy, depigmentation)Scores: 0 = absent, 1 = mild, 2 = moderate, 3 = severeMean changes not reported.Hyperkeratosis:• ALA-PDT: Pre-treatment: score 0 (4), score 1 (13),score 2 (3); Post-treatment: score 0 (20)• CP: Pre-treatment: score 0 (3), score 1 (12), score 2(3), score 3 (2); Post-treatment: score 0 (15),score 1 (5)• No significant difference between the 2 groupsbefore treatment• At end of treatment, CP scores were higher, butboth groups showed improvement; significantdifferences between groups (p < 0.05)• At 6 months: ALA-PDT: score 0 (18), score 1 (2);CP score 1 (18), score 2 (2), significant differencebetween groupsAtrophy:• ALA-PDT: Pre-treatment: score 1 (7), score 2 (11),score 3 (2); Post-treatment: score 0 (19), score 1 (1)• CP: Pre-treatment: score 1 (9), score 2 (10), score 3(1); Post-treatment: score 0 (13), score 1 (7)• No significant difference between the 2 groupsbefore treatment• At end of treatment, scores of CP were higher, butboth groups showed improvement, differencesignificant (p < 0.05)• At 6 months: ALA-PDT: score 0 (16), score 1 (4);CP: score 1 (12), score 2 (7), score 3 (1), significantdifference between groupsALA-PDT:• Pain (n not reported)• Redness and swelling(6) after lightirradiation in the firstsession, graduallyfaded away in 3 daysfor all cases except1 which developedinto erosion thefollowing day.Treated withmupirocin ointmentfor 1 week.CP:• No observed adverseevents6 monthsALA-PDT:14/20 (70%) completeresponse4 (20%) partial response2 (10%) minimalresponseClobetasol propionate:7/20 (35%) completeresponse6 (30%) partial response7 (35%) minimalresponse.Rate of completeresponse in theALA-PDT group wasmuch higher than thatin the CP group(p < 0.05, χ2 = 4.912)Rate of relapse:All patients finished the6-month follow-up.In ALA-PDT group:1 out of 14 (7.1%)patients relapsed onemonth after completionof treatment. Theremaining 13 patientsshowed no signs ofrecurrence duringfollow-up.In CP group, 7 out of 7(100%) patientsrelapsed one monthafter treatment.SomeconcernsDermato 2024, 4 155Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasShi2016 [37] 4051.4 ± 15.6(range notreported)VulvaALA-PDT (20): 10%5-aminolevulinic acidphotodynamic therapy(ALA-PDT) cream applied tothe lesions with a 1-cm marginand incubated for 3 h. Thelesions were irradiated with100 J/cm2 633 nm red light at100 mW/cm2. The same PDTprocedure was repeated3 times at 2-week intervals.CP (20): Topical 0.05%clobetasol propionateointment applied by thepatient nightly for 8 weeks.Sclerosis:• ALA-PDT: Pre-treatment: score 1 (7), score 2 (9),score 3 (4); Post-treatment: score 0 (18), score 1 (2)• CP: Pre-treatment: score 1 (7), score 2 (12), score 3(1); Post-treatment: score 0 (12), score 1 (8)• No significant difference between the 2 groupsbefore treatment• At end of treatment, scores of CP were higher, butboth groups showed improvement, withsignificant difference between the groups (p < 0.05)• At 6 months: ALA-PDT: score 0 (16), score 1 (4);CP: score 1 (15), score 2 (5), significant differencebetween groupsDepigmentation:• ALA-PDT: Pre-treatment: score 1 (7), score 2 (11),score 3 (2); Post-treatment: score 0 (14), score 1 (6)• CP: Pre-treatment: score 1 (8), score 2 (11), score 3(1); Post-treatment: score 0 (7), score 1 (13)• No significant difference between the 2 groupsbefore treatment• At end of treatment, scores of CP were higher, butboth groups showed improvement with significantdifference between both groups (p < 0.05)• 6 months: ALA-PDT: score 0 (13), score 1 (7); CP:score 1 (13), score 2 (4), score 3 (3), significantdifference between groupsALA-PDT:• Pain (n not reported)• Redness and swelling(6) after lightirradiation in the firstsession, graduallyfaded away in 3 daysfor all cases except 1which developed intoerosion the followingday. Treated withmupirocin ointmentfor 1 week.CP:• No observed adverseevents6 monthsALA-PDT:14/20 (70%) completeresponse4 (20%) partial response2 (10%) minimalresponseClobetasol propionate:7/20 (35%) completeresponse6 (30%) partial response7 (35%) minimalresponse.Rate of completeresponse in theALA-PDT group wasmuch higher than thatin the CP group(p < 0.05, χ2 = 4.912)Rate of relapse:All patients finished the6-month follow-up.In ALA-PDT group:1 out of 14 (7.1%)patients relapsed onemonth after completionof treatment. Theremaining 13 patientsshowed no signs ofrecurrence duringfollow-up.In CP group, 7 out of 7(100%) patientsrelapsed one monthafter treatment.SomeconcernsDermato 2024, 4 156Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasShi2016 [37] 4051.4 ± 15.6(range notreported)VulvaALA-PDT (20): 10%5-aminolevulinic acidphotodynamic therapy(ALA-PDT) cream applied tothe lesions with a 1-cm marginand incubated for 3 h. Thelesions were irradiated with100 J/cm2 633 nm red light at100 mW/cm2. The same PDTprocedure was repeated3 times at 2-week intervals.CP (20): Topical 0.05%clobetasol propionateointment applied by thepatient nightly for 8 weeks.Changes in symptom scores (pruritus, burning and painfeeling)• ALA-PDT: Pre-treatment: score 1 (5), score 2 (10),score 3 (5); Post-treatment: score 0 (14), score 1 (4),score 2 (1)• CP: Pre-treatment: score 1 (4), score 2 (14), score 3(2); Post-treatment: score 0 (7), score 1 (11), score 2(2)• No significant difference between the 2 groupsbefore treatment• At end of treatment, CP scores were higher, butboth groups showed improvement with significantdifferences between both groups (p = 0.035)• 6 months: ALA-PDT: score 0 (13), score 1 (4), score2 (3); CP: score 1 (2), score 2 (10), score 3 (8), withsignificant differences between the groupsMean reduction in lesion size:• ALA-PDT: 35.18 ± 3.51 cm2 → 5.38 ± 8.98 cm2 (p= 0.000)• CP: 36.29 ± 13.23 cm2 → 9.83 ± 8.51 cm2 (p =0.000)• Both groups showed significant reduction in lesionsize initially, although there was no differencebetween the 2 groups (p = 0.116)• 6 months: no significant change in ALA-PDT (p =0.523), but increase in CP (p = 0.000), with thedifference between the 2 groups statisticallysignificant (5.66 ± 8.73 cm2 vs. 32.49 ± 12.71 cm2)(p = 0.000)ALA-PDT:• Pain (n not reported)• Redness and swelling(6) after lightirradiation in the firstsession, graduallyfaded away in 3 daysfor all cases except 1which developed intoerosion the followingday. Treated withmupirocin ointmentfor 1 week.CP:• No observed adverseevents6 monthsALA-PDT:14/20 (70%) completeresponse4 (20%) partial response2 (10%) minimalresponseClobetasol propionate:7/20 (35%) completeresponse6 (30%) partial response7 (35%) minimalresponse.Rate of completeresponse in theALA-PDT group wasmuch higher than thatin the CP group(p < 0.05, χ2 = 4.912)Rate of relapse:All patients finished the6-month follow-up.In ALA-PDT group:1 out of 14 (7.1%)patients relapsed onemonth after completionof treatment. Theremaining 13 patientsshowed no signs ofrecurrence duringfollow-up.In CP group, 7 out of 7(100%) patientsrelapsed one monthafter treatment.SomeconcernsDermato 2024, 4 157Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasShi2016 [37] 4051.4 ± 15.6(range notreported)VulvaALA-PDT (20): 10%5-aminolevulinic acidphotodynamic therapy(ALA-PDT) cream applied tothe lesions with a 1-cm marginand incubated for 3 h. Thelesions were irradiated with100 J/cm2 633 nm red light at100 mW/cm2. The same PDTprocedure was repeated3 times at 2-week intervals.CP (20): Topical 0.05%clobetasol propionateointment applied by thepatient nightly for 8 weeks.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: Pre-treatment: score 1 (2), score 2 (8),score 3 (5), score 4 (5); Post-treatment: score 0 (14),score 1 (4), score 2 (2)• CP: Pre-treatment: score 1 (1), score 2 (7), score 3(10), score 4 (2); Post-treatment: score 0 (7), score 1(11), score 2 (2)• Overall, ALA-PDT was more effective in reducingthe ratios of vulvar surface affected by VLS after 8weeks of treatment; however the differencebetween both groups was not significant(p = 0.057)• 6 months: CP scores much higher than ALA-PDTand returned to a distribution profile similar tothat seen before treatment (p = 0.414). The scoresof the ALA-PDT group was similar to those at theend of treatment (p = 0.317) and lower than thosebefore treatment (p = 0.000).ALA-PDT:• Pain (n not reported)• Redness and swelling(6) after lightirradiation in the firstsession, graduallyfaded away in 3 daysfor all cases except 1which developed intoerosion the followingday. Treated withmupirocin ointmentfor 1 week.CP:• No observed adverseevents6 monthsALA-PDT:14/20 (70%) completeresponse4 (20%) partial response2 (10%) minimalresponseClobetasol propionate:7/20 (35%) completeresponse6 (30%) partial response7 (35%) minimalresponse.Rate of completeresponse in theALA-PDT group wasmuch higher than thatin the CP group(p < 0.05, χ2 = 4.912)Rate of relapse:All patients finished the6-month follow-up.In ALA-PDT group:1 out of 14 (7.1%)patients relapsed onemonth after completionof treatment. Theremaining 13 patientsshowed no signs ofrecurrence duringfollow-up.In CP group, 7 out of 7(100%) patientsrelapsed one monthafter treatment.SomeconcernsDermato 2024, 4 158Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasLi 2004 [38] 31 38.5 VulvaFocused ultrasound therapy• Frequencies of thetransducer ranged from5 to 8 MHz• Number of sessions notspecifiedResponse measured based on the reduction of pruritus,changes of the skin elasticity and color, decreasedpercentage of the involved area, and changes inhistological findingsCured: (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 SomeconcernsOral TherapiesBousema1994 [39] 78 NR (18-83) VulvaExperimental group (22):Acitretin 30 mg once daily for16 weeks, could be reduced to20 mg once daily in case ofadverse reactions after 4 weeks(AC)Control group (24): Placebo(PLA)Improvement in. . .• Pruritus: 1.0 in AC, 0.79 in PLA (p < 0.05)• Burning: 1.0 in AC, 0.85 in PLA (not significant)• Atrophic features: 0.86 in AC, 0.54 in PLA(p < 0.05)• Hyperkeratotic features: 0.76 in AC, 0.27 in PLA(p < 0.05)• Secondary features: 0.57 in AC, 0.39 in PLA (notsignificant)• Extent of lesions: 0.36 in AC, 0.08 in PLA (p < 0.05)• Higher number of responders in AC (0.64) thanPLA (0.25) (p < 0.05)• Greater degree of patient satisfaction in AC(p < 0.05):◦ Completely satisfied: 0.38 in AC, 0.18 inPLA◦ Partially satisfied: 0.51 in AC, 0.41 in PLA◦ Not satisfied: 0.08 in AC, 0.38 in PLACheilitis and xerosis in allAC patients, 1/3 of PLApatientsSevere peeling of palms andsoles in AC group (11)Increased hair loss higher inAC (23) than PLA (2)16 weeks None LowconcernDermato 2024, 4 159Table 1. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasPsychological CounsellingVittrup2022 [40] 158Median, IQRInterventiongroup: 53(33.2–60.5)Median, IQRTreatmentGroup: 50.5(30.8–57.0)VulvaControl group: usualmanagement where womanwould receive oral instructionat diagnosis, treatment, andconsultation with nursespecialized in vulvar diseasesto follow-up regardingcompliance, adherence andsupport (80)Usual treatment +psychosexual counsellinggroup offered 8 individualsessions of 45 min ofcounselling based onindividual needs (78)Female Sexual Function Index-FSFI Scores:• Control group effect size, difference from baselineto follow up: 0.4 (−1.2 to 2.0)• Intervention group effect size, difference frombaseline to follow up: 5.4 (3.2 to 7.7)Dermatology Life Quality Index-DLQI Scores:• Control group effect size, difference from baselineto follow up: −0.4 (−1.5 to 8.0)• Intervention group effect size, difference frombaseline to follow up: −2.5 (−3.7 to −1.3)WHO-5 Wellbeing Index Scores:• Control group effect size, difference from baselineto follow up: 1.0 (−3.2 to 5.1)• Intervention group effect size, difference frombaseline to follow up: 6.4 (2.3 to 10.5)Effect size of sexual counselling on sexual activity:• Control, sexually active-effect size difference:−0.6 (−2.7 to 1.6)• Intervention, sexually active–effect size difference:3.5 (0.5 to 6.4)• Control, non-sexually active–effect size difference:2.0 (−0.5 to 4.4)• Intervention, non-sexually active–effect sizedifference 8.2 (4.8 to 11.5)None 6 months Not applicable to thisstudyLowconcern* Signifies statistical significance.Dermato 2024, 4 1603.2. Risk of BiasA risk of bias analysis showed that 16 of the included studies had a low risk of bias,14 had a moderate risk of bias, and 1 had a high risk of bias (Figure 2).Dermato 2024, 4, FOR PEER REVIEW 25 3.2. Risk of Bias A risk of bias analysis showed that 16 of the included studies had a low risk of bias, 14 had a moderate risk of bias, and 1 had a high risk of bias (Figure 2). Figure 2. Risk-of-bias assessment of included studies. Low risk of bias is represented by a green circle with a “+” symbol, moderate risk of bias by a yellow circle with a “?” symbol, and high risk of bias with a “−“ symbol [14–44]. Unique ID Randomization processDeviations from intended interventionsMissing outcome dataMeasurement of the outcomeSelection of the reported resultOverallVirgili 2013Laino 2013D'Antuono 2011Goldstein 2015Corazza 2016Borghi 2015Terras 2014Virgili 2014Burkett 2021Mitchell 2021Goldstein 2011Goldstein 2019Gunthert 2022Bizjak Ogrinc 2019Cattaneo 1996Bousema 1994Funaro 2014Zivanovic 2024Krause 2023Salgado 2023Virgili 2013 (2)Tedesco 2020Shi 2016Lindhagen 1996Li 2004Sideri 1994Bracco 1993Guo 2022Vittrup 2022Gutierrez‐Ontalvilla 2022Ioannides 2010??+?+++++++++++++++++??++++++?+++++++++++—+++++++++?++?+++++++++++++++++++++++++++++??++?+???++++++++++++++?++?+??????+?+++++++++++++??+++++!!!!!!!!!++++—+++++++!!+!++!+++++++?+?+!++ + + + +i re 2. is -of- ias assess e t of i cl e st ies. o ris of ias is re rese te a reecircle, moderate risk of bias by a yellow circle, and high risk of bias by a red circle [14–44].Dermato 2024, 4 161Table 2. Management of LS in Male Patients.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality Response Adverse EventsFollow UpDurationRemission orRecurrence Risk of BiasLindhagen1996 [41] 30 NR PenisGroup 1 (15): ClobetasolpropionateGroup 2 (15): PlaceboClobetasol Propionate:Improvement: n = 10 (+7 from placebogroup who were switched)No effect: n = 3Withdrawal: n = 2Placebo:Improvement: n = 7No effect: n = 7 (subsequently givenclobetasol propionate and improved)Withdrawal: n = 1NR 6 monthsNo information about relapseor complete remissionprovided.Low concernLaino2013 [42] 28 NR (25–65) PenisGroup 1 (14): Subdermalpolydeoxyribonucleotideinfiltration, 8 sessions total, inassociation with nightlyclobetasol propionate 0.05%(PDRN) for 4 monthsGroup 2 (14): Clobetasolpropionate 0.05% nightly (CP)for 4 monthsChange in median value of. . .• Investigator Global Assessment(IGA): 4 in PDRN (p = 0.001), 1 inCP (p = 0.001)• Dermatology Life Quality Index(DLQI): 8 in PDRN (p = 0.001),4 in CP (p = 0.003)• In PDRN, 9 patients (64.3%) had areduction of at least 50% in IGAafter therapy (p = 0.007); in CP,only 2 patients (14.3%) had areduction of at least 50%• In PDRN, 7 patients (50%) had areduction of at least 50% in DLQIafter therapy; in CP, 0 patientshad a reduction of at least 50%None 6 months PDRN: 14 remission, 0 relapseCP: 8 remission, 6 relapse Some concernsDermato 2024, 4 162Table 2. Cont.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality Response Adverse EventsFollow UpDurationRemission orRecurrence Risk of BiasIoannides2010 [43] 51For controlgroup: 57.79(38–75)For treatmentgroup:56.56 (38–74)MalegenitaliaTreatment (34): systemicacitretin 35 mg daily for 20weeksControl (17): placebo capsules(identical in size and color toacitretin) for 20 weeksTwo patients, 1 on acitretin and 1 onplacebo, withdrew from the study dueto disease associated complications(phimosis) which demanded surgicalmanagementMean change in total clinician score(TCS)• Acitretin group (33): 9.39 (95% CI9.13–9.66) at baseline → 7.94 (95%CI 7.52–8.35) at week 8, and 6.00(95% CI 5.12–6.88) and 4.55 (95%CI 3.14–5.95) at weeks 16 and 20.Treatment cessation resulted in asubsequent increase in mean TCSfrom 4.55 to 6.24 (95% CI4.96– 7.52) after 16 weeks• Control group (16): 9.25 (95% CI8.94 –9.56), 9.56 (95% CI9.05–10.08), 9.25 (95% CI8.33–10.17) and 9.31 (95% CI 7.54–11.08) at weeks 0, 8, 16 and 20.• The mean TCS of the acitretingroup was significantly lowerthan that of the control group atweek 20 (p= 0.00 < 0.5).Mean change in total quality of life• Acitretin group: 12.27 (95% CI11.44 –13.10) at week 0 → 6.76(95% CI 5.37– 8.15) at week 20,which reflects a statisticallysignificant difference (p < 0.05)• Control group: 11.94 (95% CI10.65–13.22) at week 0 → 10.63(95% CI 8.85–12.40) at week 20,which is not statisticallysignificantAcitretin group:• Cheilitis (25/33)• Skin peeling (16/33)• Pruritus (10/33)• Paronychia (8/33)• Hair shedding (7/33)• Rhinitis (7/33)• GI disturbances (3/33)• Moderatehyperlipidemia (14/33)• Slight increase in liverenzymes (9/33)Control group:• GI disturbances (4/16)• Headaches (3/16)• Pruritus (2/16)• Fatigue (2/16)• Dizziness (2/16)• Arthralgias (1/16)36 weeksComplete response:36.4% (12 of 33) of the subjectson acitretin and 6.3% (12 of 16)of controlsPartial response: 36.4% (12 of33) of the treatment group andin 12.5% (2 of 16) of the controlgroup.Disease remained stable in:21.2% (7 of 33) of the acitretingroup and 31.3% (5 of 16) ofthe control groupsDisease progression: 6.1% (2 of33) of individuals on acitretinand 50.0% (8 of 16) on placeboLow concernDermato 2024, 4 1633.3. Topical Corticosteroids as a Single ModalityUnimodal topical corticosteroid therapy was the most commonly reported treatmentmodality for LS, with one male and four female studies uniquely discussing its usage.All studies noted the usage of high or very high potency topical corticosteroids, notablymometasone furoate 0.1% (MF) and clobetasol propionate 0.05% (CP). Each of the studiesthat evaluated the efficacy of topical corticosteroids for the treatment of LS interpreted re-sponse as clinical or symptomatic improvement of the affected areas. For instance, Cattaneoet al. described significant improvements in a cohort of 32 patients with vulvar LS, whereby24 weeks of treatment with CP led to significant reductions in the cumulative symptom andgross aspect scores, evident reductions in hyperkeratosis and sclerosis, and the disappear-ance of erosions and purpura. Histological parameters were also significantly improved,with twelve biopsies showing complete regression of LS findings with improvement inthe remaining patients, and overall improvements in inflammatory infiltrates, edema, andfibrosis [41]. Moreover, Lindhagen examined the efficacy of CP in male children withpenile LS, and found that, at baseline, patients were more likely to respond to CP thanplacebo, and that patients initially in the placebo arm then treated with CP responded toCP therapy [15].Three studies performed comparisons of topical corticosteroid therapy in the treatmentof females with LS. Corazza et al. compared CP and MF, two high potency topical steroids,as twice weekly maintenance therapy in patients who had already achieved disease stabilitywith a course of topical corticosteroids, and found no significant differences in outcomesbetween the two groups over a 52-week period [16]. Virgili et al. also compared CP and MF,and similarly concluded that CP and MF were equally effective for treatment of LS, withthe decrease in mean sign and symptom scores significant amongst both groups withoutsignificant differences between the groups [17]. Finally, Borghi et al. looked at MF alone,either in the form of a tapering (five days weekly for four weeks, alternate days for fourweeks, twice weekly for four weeks) or continuous (five days per week) regimen, andfound no statistically significant difference between the two treatment cohorts, concludingthat both a tapering and continuous regimen were effective [19].Overall, high potency topical corticosteroids recurrently proved to be effective inthe symptomatic and physical management of LS in both males and females, and shouldremain the gold standard of therapy for genital LS therapy. There were no significantdifferences between corticosteroid subtypes, as well as no differences in patient outcomeswith regards to varying treatment regimens, allowing physicians to prescribe the course oftherapy that the patient feels most comfortable with.3.4. Topical Corticosteroids and Adjunct AgentsAn additional three studies (two female studies, one male study) discussed the useof topical corticosteroids, however these studies attempted to use steroid therapy in con-junction with adjunct agents. A study by D’Antuono et al. analyzed the potential forclothing therapy in the management of vulvar LS, comparing Dermasilk or cotton briefs inconjunction with CP and a vitamin E moisturizer [29]. While both groups had relief fromsoreness and pruritus, the Dermasilk group showed significant improvement in burningsoreness and pruritus. The Dermasilk was also noted to have a greater, non-significantimprovement in dyspareunia. Moreover, the severity of these symptoms was in favour ofthe Dermasilk group with regards to overall improvement and speed of reduction withinfour weeks. In terms of clinical signs, there was a significantly better improvement inerythema and a non-significant greater improvement in whitening in the Dermasilk group.Another study analyzed the impact of CP, this time in conjunction with traditionalChinese medicine soaking and washing for 3–4 months, whereby the combination ofChinese and Western medicine has been shown to enhance curative effects, decreaseadverse events, and improve the quality of life of vulvar LS patients [45]. More specifically,the traditional Chinese medicine soaking and washing regimen consisted of Fructus cnidiiand sweet wormwood, however, elaboration pertaining to the specifics of the treatment planDermato 2024, 4 164was not provided [46]. Fructuss cnidii is commonly used in the treatment of chronic itch [46],while sweet wormwood has a therapeutic value in inflammatory diseases and autoimmunedisorders [42]. Guo et al. found that there was a statistically significant reduction inpruritus when CP was combined with traditional Chinese medicine. Differences in skinelasticity, colour, and disease extent were not significant, with easy relapse after treatmentcompletion [45]. Overall, patients were found to have better outcomes with multi-focusedlaser treatment (see “Energy-Based Devices” section).Laino et al. evaluated the efficacy of polydeoxyribonucleotide (PDRN) administered in-tradermally in conjunction with topical CP, as compared to CP monotherapy [42]. The studyfound that PDRN + CP patients achieved better improvements than the CP monotherapygroup, as well as better improvements in elasticity and decreased ecchymoses, infiltratingareas, erythematous areas, fissures, and lichenification. Moreover, PDRN + CP patients sawa significant reduction in Investigator Global Assessment (IGA) scores and DermatologyLife Quality Index (DLQI) scores, and maintained disease control at six months, while theCP patients demonstrated more signs of disease relapse at the 4–6 months follow up [20].Altogether, while topical corticosteroids continuously prove to be efficacious in themanagement of LS, certain adjunct therapies have also proven to improve patient out-comes, and should be utilized in the clinical setting. Notably, silk briefs, traditional Chinesemedicine soaks, and PDRN can be used in conjunction with high potency topical corticos-teroids to provide patients with additional relief from their LS-associated symptoms.3.5. Steroid-Sparing Topical AgentsSeven studies reported on the use of steroid-sparing topical therapies for the treatmentof female patients with LS. Two reported on topical calcineurin inhibitors. Funaro et al.compared the efficacy of topical tacrolimus 0.1% to CP in patients with vulvar LS [21],and found significant decreases in papules, atrophic and erythematous patches, erosions,and ulcerations across in both groups. The CP group saw a more significant decrease inpapules and atrophic patches than the tacrolimus group, and by the end of the study thenumber of patients with no clinical signs or reported symptoms was significantly higherin the CP group in comparison to the tacrolimus group, with Visual Analog Scale (VAS)scores reporting that CP was more effective than tacrolimus in reducing burning, pain, andpruritus [21]. Similar to tacrolimus, while pimecrolimus also appeared to be effective in themanagement of LS, CP showed a more robust clinical response [22]. While histopathologicalimprovement in inflammation was significant for both CP and pimecrolimus groups, acomparison demonstrated a superior improvement in the CP group, and numerically morenon-responders in the pimecrolimus group (n = 8) than the CP group (n = 1) [22]. However,VAS scores showed improvement in both groups, with a numerically greater improvementin the CP group, while IGA scores and subscales denoting disease severity, lichenification,and ulceration were equivalent between the two groups [22].The efficacy of topical hormonal therapy was also investigated. Testosterone 2% oint-ment as maintenance therapy for vulvar LS, in patients who had already achieved diseasecontrol with CP, showed less-than-promising results [41]. Four (25%) patients experiencedburning upon ointment application, while nine (56%) noted symptom recurrence, mainlypruritus. Overall, there was a statistically significant worsening of symptoms, whereby pa-tients kept on CP reported further improvements in symptoms [41]. A study by Sideri et al.found that topical testosterone propionate was as effective as petroleum ointment in themanagement of vulvar LS, with no significant differences between the two groups [23]. Top-ical progesterone 8% ointment was also found to be inferior to CP treatment in managingLS clinical signs and symptoms [24]. Notably, there was less improvement in standardizedLS clinical (p < 0.05), symptom (p = 0.095), and physical scores in progesterone patients asopposed to CP patients, and biopsies proved that more CP patients (81%) achieved diseaseremission in comparison to progesterone patients (60%) [24]. Interestingly, there were norandomized controlled trials investigating the efficacy of topical estrogen cream in thetreatment of vulvar LS, despite being a widely recommended modality. Finally, a study con-Dermato 2024, 4 165ducted by Bracco et al. compared topical CP, testosterone, progesterone, and a cream-basedpreparation, and concluded that significant differences in gross and histologic changesbefore and after treatment were only observed with CP, and that CP-treated patients noteda much lower degree of patients with unchanged symptoms (CP 10%, testosterone 40%,progesterone 50%, cream-based preparation 69%), reinforcing CP as the mainstay of therapyfor vulvar LS [25].Human fibroblast lysate (HFL) cream, which contains multiple anti-inflammatorycytokines and wound-healing growth factors, did not show statistically significant differ-ences in comparison to placebo [18]. Histopathological analysis revealed no significantchanges after 12 weeks of therapy. Finally, Virgili et al. analyzed a cohort of patients whohad achieved LS disease remission with the once-daily application of MF, who now soughtdisease maintenance with either MF twice weekly, topical vitamin E oil once daily, or coldcream once daily [26]. The study showed that MF applied twice weekly protected patientsfrom relapsing in comparison to daily topical vitamin E or cold cream applications overthree months [26]. Further studies by Virgili et al. showed that vulvar LS in remission fromtopical corticosteroid treatment may be managed with either vitamin E or emollient therapy,however, relapse rates are high at 52 weeks, with cumulative modified crude relapse ratesbetween 50 and 55% [27].In summary, while certain steroid-sparing topical agents may prove to be effective inthe management of genital LS, they are suboptimal in comparison to topical corticosteroids,and should thus not be used as a first-line treatment. Other modalities, namely topicalhormonal therapies, HFL cream, and vitamin E oils, are not effective tools in managinggenital LS and should not be used.3.6. Intradermal InjectionsIntradermal injections were reported by three studies in the literature. Platelet-richplasma (PRP) and nanofat infiltrations delivered twice at a three-month interval for patientswith moderate-to-severe vulvar LS were noted to have no significant improvement in vulvarskin elasticity, however, patients noted a significant improvement in symptoms such asitching, pain, burning, and dyspareunia [28]. Objectively, there was noted improvement inclinical signs such as cervical erosions, fissures, stenosis, and leukoderma, and a significantdecrease in all inflammatory cell types upon analysis of skin biopsies [28]. Importantly,when Gutierrez-Ontalvilla et al. compared the PRP group to the CP group, they foundsignificant improvements in the PRP group with regards to fissures, stenosis, pallor, itching,burning, and dyspareunia, which were not achieved in the CP group, and treatmentoutcomes continued to be significantly more effective in the PRP group with regards toreduction in erosions, fissures, stenosis, and pallor at one-year follow-up, with no cases ofrelapse [28]. Moreover, histological evaluations and quality-of-life assessments (using theSkindex-29 questionnaire) also revealed statistically significant positive findings for thePRP group in comparison to the CP group [28]. However, Goldstein et al. also investigatedthe potential for PRP injections administered twice, six weeks apart, in the managementof vulvar LS, but found more variable results, whereby 5 patients saw improvement inthe histopathologic inflammation between pre- and post-treatment biopsies, 10 had nochange, and 4 had more inflammation [44]. The mean difference in the Clinical ScoringSystem for Vulvar Lichen Sclerosus for the PRP and placebo groups was insignificant [44].Finally, Tedesco et al. evaluated the efficacy of intradermally injected adipose tissue-derivedstromal vascular fraction either as monotherapy or in conjunction with PRP, and found thatboth treatments were equally efficacious in all patients with the exception of those withlate-stage disease (Table 3) [30].Dermato 2024, 4 166Table 3. Management of LS in both female and male patients.#PatientsMean Age(Age Range)AffectedRegion Treatment Modality ResponseAdverseEventsFollow UpDurationRemission orRelapseRisk ofBiasTedesco2020 [44]40 (24 M,16 F)Entire sample:43 (18–78)Female patients:59 (29–78)Male patients:49 (18–76)Female andmalegenitalia,nototherwisespecifiedGroup 1 (20 total, 5F and 15M):Intradermal injection ofadipose tissue derived-stromalvascular fraction; 2 surgicalprocedures 4 months apartGroup 2 (20 total, 11F and 9M):Intradermal injection ofcombined purified AD-SVFand platelet rich plasma (PRP);2 surgical procedures 4months apartMean clinical score at 6 months post-second injection(score ranging from 0 (disease stability) to 3 (greatfunctional improvement with reduction of symptomsuntil their disappearance) based on subjective itch,pain, burning sensation and dyspareunia on 10 levelVAS)• AD-SVF: 2.0 +/− 0.8, AD-SVF + PRP:1.8 +/− 1.1• No statistically significant difference betweenboth groups (p = 0.42)• Separate analysis of both arms based onpatients with early vs. late LS revealedsignificant difference for AD-SVF + PRP but notfor AD-SVF.◦ For AD-SVF + PRP: patients with early LS(7: 3F, 4M) had mean score of 2.6 +/− 0.7 ofcompared to patients with late LS (13, 8F, 5M)who had mean score of 1.3 +/− 1.0 (p = 0.011)◦ For AD-SVF: patients with early LS (10, 1F and9M) had mean score of 2.0 +/− 0.8 compared topatients with late LS (10, 4F and 6M) who hadmean score of 2.0 +/− 0.9 (p = 0.77)• Analysis of patients with early vs. late LS alsorevealed significantly higher clinical scorescompared to late-stage patients(early = 2.2 +/− 0.8, late = 1.6 +/− 1.0, p = 0.046)• No significant differences in clinical scorebetween male and female patients(F = 2.0 +/− 1.1; M = 1.79 +/− 0.9, p = 0.52)Mean change in QoL (based on DLQI questionnaire)• Significant improvement in QoL after 6 monthsfor both groups (p = 0.0002) with median DLQIvalue decreased from 5.0 +/− 3.9 (moderateimpact) to 2.32 +/− 1.85.·• Individual subgroup analysis also revealedsignificant improvement of QoL for each group·• Separate analysis based on disease stagerevealed better results in patients with early LStreated with AD-SVF + PRP than inAD-SVF-treated patients (−4.7 +/− 2.8 vs.−1.7 +/− 2.2, p = 0.036)• Overall significant difference in QoL amongearly and late-stage patients treated withcombinatory therapy (−4.7 +/− 2.8 vs.−1.3 +/− 2.0, p = 0.0083)None 6 months13 patients had completeresolution of symptoms23 showed significantimprovement in symptoms4 showed no changes2 reported a reduction of whitelesionsSomeconcernsDermato 2024, 4 167Overall, the efficacy of PRP in the management of LS would require further inves-tigation given the variability of data currently available in the literature among onlytwo randomized controlled trials, while adipose tissue-derived stromal vascular fractionsas either monotherapy or in conjunction with PRP have the potential to provide early stageLS patients with symptomatic relief.3.7. Energy-Based DevicesThe use of energy-based devices was reported by 10 studies in females with LS. Guoet al. compared carbon dioxide (CO2) laser therapy and photodynamic therapy (PDT) using5% 5-aminolevulinic acid (5-ALA) as a photosensitizer, and found that CO2 treatment led tostatistically significant improvements in pruritus, skin elasticity and colour, lesion size, andtotal clinical scores, while 5-ALA PDT produced significant improvements in the degreeof pruritus, skin colour, and total clinical scores [45]. Notably, significant differences wereobserved between the groups at three months post-treatment, with the study indicatingthat CO2 laser therapy has the most potential to improve clinical signs and symptoms andprevent relapse within two months [45]. CO2 lasers were used on two other occasionsin the literature, and also demonstrated good efficacy in comparison to CP. Burkett et al.showed that patients treated with a CO2 laser had greater improvement in their Skindex-29 scores at six months in comparison to CP treatment [31]. The patients also viewedtheir treatment outcomes more positively, with more CO2-treated patients feeling a betterimprovement in their symptoms (89% vs. 62%) and feeling satisfied with their treatment(81% vs. 41%) [31]. Differently, Mitchell et al. placebo-controlled their CO2 laser therapytrial, and found insignificant improvements in LS upon histopathological examinationwhen comparing the CO2 and placebo lasers [32]. Similarly, patient scores according tothe Clinical Scoring System for Vulvar Lichen Sclerosus showed improvement, but thedifference in comparison to the placebo group was insignificant, while physician scoringscales also did not demonstrate significant change in either treatment arm [32]. Additionally,Krause et al. investigated the impact of a CO2 laser’s dose on clinical improvement in LSscores, and found that higher dosages show no significant benefit with regards to LS scores,visual analog scores, sexual activity, or quality of life when compared to lower doses [33].Other energy-based devices reported for LS include the non-ablative neodymium:yttriumaluminum garnet (Nd:YAG) laser and ultraviolet A (UVA) phototherapy. Bizjak Ogrincet al. studied the efficacy of the Nd:YAG laser in comparison to topical corticosteroids,and found that while patients in both groups experienced a reduction in itching, burning,and pain intensity, the reduction was statistically significantly better for patients in theNd:YAG laser group amongst all symptoms, and numerically more patients treated withthe Nd:YAG laser remained disease-free at a three-month follow up (40% vs. 0%) [33].Patients also experienced a greater degree of satisfaction when treated with laser therapy(100% very satisfied, compared to 12.5% in the topical steroid group). Zivanovic et al.assessed the efficacy of a combined Nd:YAG/Er:YAG laser in comparison to topical CP,concluding that total LS scores decreased significantly in both groups [35]. CO2 lasers werealso compared to topical CP by Salgado et al., who noted similar findings: post-treatmentvulvar characteristics and impact on quality of life did not differ significantly between thetwo groups, while laser-treated patients had a greater degree of satisfaction [36]. Lightwas also tried as a treatment modality for LS in two studies. Terras et al. investigatedthe efficacy of UVA phototherapy compared to CP in the management of LS, and foundthat both therapies resulted in significant decreases in total clinician’s scores, which tookinto account hypopigmentation, sclerosis, atrophy, hyperkeratosis, erosions, edema, anderythema, but the difference between the groups was not significant [37]. With regards toVAS scores, CP had more parameters that achieved statistically significant results, notablydecreases in pruritus, burning and/or pain, and the Skindex-29 score, however, only thescore for burning and/or pain significantly decreased for UVA-treated patients. Ultrasoundand histopathological assessments also noted improvements in both groups, however, onlythe values in the CP group reached significance. Shi et al. investigated the use of PDT withDermato 2024, 4 16810% 5-ALA cream as compared to CP, and found that PDT resulted in twice the responseelicited by CP in terms of hyperkeratosis, atrophy, sclerosis, and depigmentation [38].Finally, Li et al. attempted to use focused ultrasound therapy for the treatment of vulvardystrophy, including LS, with a transducer range between 5 and 8 MHz, and noted adramatic improvement in the patients’ total response rates and the tissues’ return to normalappearance by 3–6 months, with continued response/clearance of disease at the two-yearfollow-up [39].Generally, CO2 laser was often effective in comparison to other laser types and highpotency topical corticosteroids, serving as an adjunct in the genital LS treatment armamen-tarium. Importantly, higher laser doses did not prove to be more effective than lower doses.Moreover, the Nd:YAG or Er:YAG lasers or UVA therapy also proved to be either equallyeffective or more effective than topical corticosteroids with regards to objective findings,while patients treated with laser modalities typically had greater treatment satisfaction.Finally, PDT-treated patients also had greater responses in their physical LS findings thanpatients treated with topical steroids. Of great importance, laser therapy is often costlyand comes with a great out of pocket expense to patients, and thus might not be a feasibleoption for all.3.8. Oral TherapiesTwo studies analyzed the impact of oral therapy in the treatment of LS. Bousemaet al. investigated acitretin, a second-generation retinoid dosed at 20 to 30 mg daily for16 weeks [43]. While symptoms and signs improved in both the acitretin- and placebo-treated groups, sign and symptom intensity was statistically significantly lower for pruritus,atrophy, and hyperkeratosis in the acitretin group. The number of treatment-responsivepatients was also noted to be significantly higher in the acitretin group (64%) as comparedto the placebo (25%) (p < 0.05). Ioannides et al. also investigated the use of acitretin inthe management of LS compared to the placebo, but instead in cases involving the malegenitalia [40]. A larger number of acitretin-treated patients achieved complete or partialresponse compared to placebo-treated patients (36.4% and 36.4% vs. 6.3% and 12.5%).Finally, there was a significant improvement in the mean DLQI score for the acitretingroup [40].Overall, while acitretin proved to be effective in the management of genital LS, nodirect comparisons with topical corticosteroids were noted in the literature. Such a com-parison would be needed to further note the efficacy of acitretin as compared to the goldstandard in LS management, while being cognizant of the fact that only topical corticos-teroids prevent malignant progression of the disease.3.9. Psychological CounsellingVittrup et al. analyzed the impact of psychosexual counselling in addition to usual carewith ultrapotent topical corticosteroids in combination with a fatty cream and oil massage ofthe vulva [47]. After six months of therapy, the patients who had underwent psychosexualcounselling had a statistically significant improvement in their sexual functioning, asopposed to a non-significant improvement in the control group. The counselled groupachieved better improvements in their sexual function indices, mean DLQI scores, and ahigher degree of quality of life when compared to the controls, reinforcing the significantimpact that psychosexual counselling has on outcomes in LS patients [47].4. DiscussionIn 2018 the British Association of Dermatologists published the first guidelines for themanagement of LS, in which a strong recommendation was made to start all female andmale patients on topical CP [48]. In accordance with this guideline, topical corticosteroidsremain the cornerstone of LS treatment, with high potency CP and MF demonstratingsignificant efficacy in improving cumulative symptoms and gross aspect scores in fourRCTs [16,17,19,41]. Importantly, results from two RCTs, which compared CP and MF,Dermato 2024, 4 169showed no significant differences in effectiveness, suggesting that the two high-potencycorticosteroids could be considered interchangeable for vulvar LS management, how-ever, the above-mentioned guidelines do not mention the use of MF as an alternative toCP [16,17,48]. As for penile LS, despite the current guideline recommendation to initiate CPin males, only one RCT, which looked at the efficacy of unimodal therapy with CP comparedto that of CP combined with subdermal injections of PDRN, was identified [20]. Finally,CP combined with other modalities, such as Dermasilk briefs and vitamin E moisturizers,showed promising results in symptom relief and clinical outcomes [26,29].This review also identified several steroid-sparing topical agents and alternativetherapies for LS management. Topical calcineurin inhibitors demonstrated some efficacycomparable to corticosteroids in improving symptoms and clinical signs, providing alterna-tive treatment options, especially for patients who may be intolerant to corticosteroids orrequire long-term maintenance therapy. However, results from two RCTs suggest topicalsteroids remain superior [21,22]. Current guidelines conclude there is insufficient evidenceto recommend the use of these therapies [48], and, thus, further research is warranted.An additional important consideration is the relatively high cost of these medicationscompared to that of topical corticosteroids.The efficacy of hormonal therapies, such as testosterone and progesterone ointments,was also investigated in four RCTs. However, the results appeared less promising comparedto corticosteroids [24,25,41]. Importantly, one study showed significant worsening ofsymptoms with topical testosterone, suggesting limited utility in LS management [41].Similarly, current guidelines do not recommend the use of topical hormonal therapy [48].However, topical estrogen has been successfully used in conjunction with CP for treatmentof LS [49–51], and this is commonly recommended by clinicians for well-controlled LS.Importantly, various studies demonstrated therapies with outcomes superior to thoseof CP. Energy-based devices, namely CO2 and Nd:YAG lasers, showed promising results inimproving symptoms and clinical outcomes, with the CO2 laser improving symptoms andquality of life more than CP, and Nd:YAG leading to a greater improvement in remissionrates at three months compared to CP [31,34]. Importantly, these RCTs were all publishedfollowing the release of the 2018 guidelines. PRP injections also demonstrated superiorefficacy compared to corticosteroids, with sustained benefits and minimal adverse effectsobserved over long-term follow-up in one study [28], however, results were variable inanother [44]. Given the variability in the reproducibility of the results, the generalization ofthe results is limited, and further research is warranted.In one RCT, oral acitretin demonstrated significant efficacy in improving symptomsand clinical signs, suggesting its potential role as an alternative or adjunctive therapy [43].Current guidelines report insufficient evidence to recommend this intervention [48]. Finally,given that multiple studies have proven that LS is associated with increased psychologicaldistress, decreased quality of life and overall negative health outcomes, more studiesevaluating the efficacy and importance of psychological intervention are paramount toimproving patients’ quality of life, in addition to pharmacologic therapies [8,52].Despite the comprehensive nature of this systematic review, there are several limi-tations. Firstly, the inclusion criteria focused exclusively on RCTs, potentially excludingrelevant studies published in other study designs. This may have resulted in the omissionof valuable data on different treatment modalities for LS. Moreover, although only RCTswere included to provide a summary of the highest level of evidence, when analyzed usingthe revised Cochrane tool for risk of bias, eleven studies out of nineteen were associatedwith “moderate risk” and one study with “high risk” of bias, which underscores the needfor cautious interpretation of the findings and highlights potential systematic errors thatcan influence the validity and reliability of the results [53]. Moreover, the heterogeneityin treatment regimens and outcome measures across studies hindered direct comparisonsbetween different modalities via a meta-analysis. Importantly, the predominance of female-focused studies in the RCT literature suggests a gap in the current understanding of LSmanagement in males, in addition to limiting conclusions that can be made from thisDermato 2024, 4 170review for this population. Finally, comparisons of the efficacies associated with varioustreatment modalities proved to be a challenge across different studies, given that a plethoraof investigator scores were used to objectify LS findings.Despite these limitations, this systematic review provides a comprehensive synthesisof the current evidence on treatment modalities for LS, serving as a valuable resourcefor clinicians and researchers in guiding clinical decision-making and future researchendeavors, and reinforcing high potency topical corticosteroids as the mainstay of treatmentfor LS with regards to the prevention of malignant progression, symptomatic management,and improvement in architectural changes. While we strongly reinforce the importance oftopical corticosteroids as the cornerstone of treatment for genital LS, more extensive researchis needed to better formulate therapeutic algorithms based on a multitude of factors.5. ConclusionsIn conclusion, while LS is reportedly difficult to treat and is known to have a sig-nificant impact on patients’ quality of life, the literature contains a plethora of potentialtreatment modalities with varying outcomes. Physicians should be aware that while topicalcorticosteroids are the mainstay of treatment, they are not the sole modality availableto manage this condition, and that multimodal therapies that combine topical steroids,clothing therapy, and procedural interventions for long-term management also prove to beeffective and tolerable.Author Contributions: Conceptualization, S.C. and I.M.; methodology, S.C. and I.M.; software,S.C., S.D.M. and M.S.; validation and formal analysis, S.C., S.D.M., M.S., A.Y., L.J., S.S. and Y.C.;investigation, S.C., S.D.M., M.S., A.Y., L.J., S.S. and Y.C.; resources, S.C., S.D.M., M.S., A.Y., L.J., S.S.and Y.C.; data curation, S.C., S.D.M., M.S., A.Y., L.J., S.S. and Y.C.; writing—original draft preparation,S.C., S.D.M. and M.S.; writing—review and editing, S.C., S.D.M., M.S., A.Y., L.J., S.S., Y.C., A.L., I.V.L.and I.M.; visualization, S.C. and I.M.; supervision, I.M., I.V.L. and A.L.; project administration, S.C.and I.M.; funding acquisition, none. All authors have read and agreed to the published version ofthe manuscript.Funding: This research received no external funding.Institutional Review Board Statement: Not applicable.Informed Consent Statement: Not applicable.Data Availability Statement: Template data collection forms are available within our manuscript;data extracted from included studies are originally available in included studies; data used for allanalyses are originally available in included studies; analytic code is not applicable and no formalanalysis occurred.Conflicts of Interest: The authors declare no conflicts of interest.References1. Radenska-Lopovok, S.G.; Potapov, A.L.; Loginova, M.M.; Elagin, V.V.; Bychkova, A.E.; Karabut, M.M.; Kuznetsov, S.S.; Asaturova,A.V.; Kuznetsova, I.A.; Apolikhina, I.A.; et al. Possibilities of multiphoton microscopy for the diagnosis of the vulvar lichensclerosus. Arkh Patol. 2023, 85, 29–39. [CrossRef] [PubMed]2. Marzec, A.; Olejek, A.; Stopinska, K.; Cnota, W.; Gabriel, I. 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Female genital lichen sclerosus is connected with a higher depressionrate, decreased sexual quality of life and diminished work productivity. PLoS ONE 2023, 18, e0284948. [CrossRef]53. Sterne, J.A.C.; Savovic´, J.; Page, M.J.; Elbers, R.G.; Blencowe, N.S.; Boutron, I.; Cates, C.J.; Cheng, H.Y.; Corbett, M.S.; Eldridge,S.M.; et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ 2019, 366, l4898. [CrossRef] [PubMed]Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individualauthor(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury topeople or property resulting from any ideas, methods, instructions or products referred to in the content.
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Treatment Modalities for Genital Lichen Sclerosus: A Systematic Review
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