Erosive lichen planus affecting the vulva and vagina (ELPV) is a rare inflammatory skin disease, presenting with painful erosions and severe scarring.1 The disease course is persistent and often refractory to treatment: up to 45% patients do not experience remission with topical treatments, while evidence for systemic treatments remains scarce.2 Hydroxychloroquine (HCQ) is frequently used in daily practice as a first choice systemic therapy.3 However, little evidence is available on HCQ for ELPV.2 The aim of this study was to analyse the effectiveness and safety of HCQ in ELPV.</p

Esajas, M D

Horváth, B

Oldhoff, J M

Rashid, H

Vermeer, H A B

English

University of Groningen

   University of GroningenThe use of hydroxychloroquine as a systemic treatment in erosive lichen planus of the vulvaand vaginaVermeer, H A B; Rashid, H; Esajas, M D; Oldhoff, J M; Horváth, BPublished in:The British journal of dermatologyDOI:10.1111/bjd.19870IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Vermeer, H. A. B., Rashid, H., Esajas, M. D., Oldhoff, J. M., & Horváth, B. (2021). The use ofhydroxychloroquine as a systemic treatment in erosive lichen planus of the vulva and vagina. The Britishjournal of dermatology. https://doi.org/10.1111/bjd.19870CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Research letterThe use of hydroxychloroquine as a systemictreatment in erosive lichen planus of the vulvaand vaginaDOI: 10.1111/bjd.19870DEAR EDITOR, Erosive lichen planus affecting the vulva andvagina (ELPV) is a rare inflammatory skin disease, presentingwith painful erosions and severe scarring.1 The disease courseis persistent and often refractory to treatment: up to 45% ofpatients do not experience remission with topical treatments,and evidence for systemic treatments remains scarce.2 Hydrox-ychloroquine (HCQ) is frequently used in daily practice as afirst choice systemic therapy.3 However, little evidence isavailable on use of HCQ for ELPV.2 The aim of this study wasto analyse the effectiveness and safety of HCQ in ELPV.Adult patients diagnosed with ELPV and treated with HCQbetween 2009 and 2020 were retrospectively analysed.Patients with insufficient clinical data, or patients who made ageneral objection to the use of their data in research wereexcluded. Informed consent was not collected, because ofanonymous data processing and lack of care regimen interfer-ence. Due to this study’s noninterventional character, the Med-ical Research Involving Human Subjects Act did not apply,and official approval by the medical ethics review committeewas not required.Clinical response was analysed using the Physician’s GlobalAssessment score. Clinical response was defined as a decreasein physical signs for at least two consecutive hospital visits. Aflare-up was defined as return to baseline disease activity orworsening of physical signs after initial response. Adverseevents (AE) were graded in severity with the Common Termi-nology Criteria for Adverse Events (CTCAE).4A total of 15 patients with ELPV treated with HCQ wereanalysed. Beforehand, five patients were excluded, because ofinsufficient clinical data (n = 4, all follow-up in a differenthospital) and HCQ being used for another indication (n = 1).The median age was 55 years (range 23–82) and 67% werepostmenopausal. The median diagnostic delay was 2 years(range 0–11). Overall, 87% (n = 13) had biopsy-provenlichen planus, nine of which were based on vulval biopsy.Other biopsy sites included the oral mucosa and skin. Orallichen planus was present in 53% (n = 8).Fourteen patients used concomitant topical treatment,mainly tacrolimus 001% ointment (47%), topical steroids(67%) and hydrocortisone/estriol vaginal creams (27%). HCQwas the first systemic treatment in 11 patients, whereas fourhad received one or more immunosuppressive drugs before,which were HCQ (n = 2), prednisolone (n = 2), methotrexate(n = 1) and ciclosporin (n = 1).In this study, HCQ dosage, dependent on disease activityand tolerance, ranged between 200 and 600 mg, with oneoutlier of 800 mg in a patient who was a ‘nonresponder’. Intotal, 60% (n = 9) responded to HCQ. At 3 months, allpatients were still on HCQ, with three patients reportingimprovement. At nine months, twelve patients were still onHCQ, with eight reporting improvement. Seven (47%)patients were still successfully on HCQ at 24 months.Reported dosages at initial response were 400 mg (n = 7) and200 mg (n = 2). Further dose–response correlations could notbe evaluated because of individual dosage fluctuations. Patientsvisited with a median 3-month interval (range 06–126). Themedian time to treatment response was 5 months (range 1–185). Median treatment duration was 238 months (range41–81). Reasons for cessation included ineffectiveness(n = 6), AE (n = 1), development of malignancy (n = 1) andloss to follow-up (n = 2).Three patients (20%) experienced disease flare-ups duringtreatment. Flare-ups resolved spontaneously or after dosageincrease after a median of 11 weeks (range 28–313). Eightpatients (53%) experienced AEs during treatment, most com-monly infections and gastrointestinal complaints. AEs resolvedafter dosage lowering or additional treatment (Table 1).Previous research has shown that ELPV is a difficult to treatcondition.2,3 This study suggests that HCQ can be an effectivetreatment in ELPV. Overall, 60% of the patients responded toHCQ, with almost half experiencing a long-term effect. AEs(53%) were mostly mild or moderate. Flare-ups (20%)resolved either after dosage increase or spontaneously.Our response rate to HCQ was higher compared with the36% success rate of a case audit review in ELPV.3 Unfortu-nately, no dosages were described, making comparison diffi-cult. Recently, Cline et al. reported a clinical improvement of70% with methotrexate in ELPV,5 exceeding our response rate.However, HCQ was better tolerated: only one patient stoppedbecause of an AE, compared with 30% from methotrexate use.Our results suggest that HCQ has a slow onset of action, asonly 20% reported improvement at 3 months, but 53% hadresponded at 9 months. The time taken to respond may beoverestimated, as data were collected retrospectively duringhospital visits.Limitations include the retrospective nature, the limitedheterogeneous sample size and use of concomitant topicalmedication.© 2021 The Authors. British Journal of Dermatologypublished by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.British Journal of Dermatology (2021) 1This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use,distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Although evidence about systemic treatment in ELPV isscarce, this study provides a broad view on treatment charac-teristics and safety of HCQ in ELPV in a daily care setting.2We conclude that HCQ can be an effective and safe treatmentin ELPV. Future studies are needed to further assess effectivesystemic treatments for ELPV.H. A. B. Vermeer iD ,1 H. Rashid,1 M. D. Esajas,2J. M. Oldhoff iD 1 and B. Horvath iD 11Department of Dermatology; and 2Department of Obstetrics andGynaecology, University Medical Centre Groningen, University of Groningen,Groningen, the NetherlandsCorrespondence: Marja Oldhoff.Email: j.m.oldhoff@umcg.nlReferences1 Lewis FM, Bogliatto F. Erosive vulval lichen planus – a diagnosisnot to be missed: a clinical review. Eur J Obstet Gynecol Reprod Biol2013; 171:214–9.2 Dunaway S, Tyler K, Kaffenberger J. Update on treatments for ero-sive vulvovaginal lichen planus. Int J Dermatol 2020; 59:297–302.3 Simpson RC, Littlewood SM, Cooper SM et al. Real-life experienceof managing vulval erosive lichen planus: a case-based review andU.K. multicentre case note audit. Br J Dermatol 2012; 167:85–91.4 U.S. Department of Health and Human services. Common Termi-nology Criteria for Adverse Events v4.0. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf (last accessed 8 March 2021).5 Cline A, Cuellar-Barboza A, Jorizzo JL, Pichardo RO. Methotrexatefor the treatment of recalcitrant erosive lichen planus of the vulva.JAMA Dermatol 2020; 2:2019–21.Funding sources: none.Conflicts of interest: B.H. reports fees from Janssen-Cilag (AdvisoryBoards, Educational grants, Consultations, Investigator Initiative Stud-ies), AbbVie (Advisory Boards, Educational grants, Consultations,Investigator Initiative Studies), Novartis Pharma (Advisory Boards,Consultations, Investigator Initiative Studies), UCB Pharma (AdvisoryBoards, Consultations), Leo Pharma (Consultations), Solenne B.V.(Investigator Initiative Studies), Celgene (Consultations, InvestigatorInitiative Studies), Akari therapeutics (Consultations, Investigator Ini-tiative Studies), Philips (Consultation), Roche (Consultation), Regen-eron (Consultation) and Sanofi (Consultation); fees were paid to theinstitution.Table 1 Treatment characteristics of 15 patients with erosive lichenplanus affecting the vulva and vaginaTreatment characteristics (n = 15) ValuesDosage in mg/day, range 200–800HCQ duration in months, median (range) 238 (41–81)Total follow-up duration in months,median (range)38 (4–123)Time until response in months, median(range)5 (1–185)Responders 9 (60)3 months 3 (20)9 months 8 (53)12 months 7 (47)24 months 7 (47)Patients with flare-ups 3 (20)Flare-up duration in weeks, median(range)11 (28–313)Concomitant topical anti-inflammatorytreatment14 (93)Topical corticosteroids 10 (67)HCA 25%/estriol vaginal cream 4 (27)Topical tacrolimus 0,1% ointment 7 (47)Intralesional steroid injections 1 (7)Experienced AE 8 (53)Hearing loss (CTCAE 3) 1 (7)Nausea (with weight loss) (CTCAE 2) 1 (7)Infection (CTCAE 2) 3 (20)Blurry vision (CTCAE 2) 1 (7)Gastrointestinal disturbances (CTCAE 1) 3 (20)Dizziness (CTCAE 1) 3 (20)Infections (CTCAE 1) 2 (13)Headache (CTCAE 1) 2 (13)Fatigue (CTCAE 1) 1 (7)Heart palpitations (CTCAE 1) 1 (7)Hair loss (CTCAE 1) 1 (7)Tinnitus (CTCAE 1) 1 (7)General malaise (CTCAE 1) 1 (7)Data are n (%) unless otherwise specified. AE adverse event;CTCAE, Common Terminology Criteria for Adverse Events(CTCAE grade 1–5: mild, moderate, severe, life-threatening,death); HCA, hydrocortisone; HCQ hydroxychloroquine.© 2021 The Authors. British Journal of Dermatologypublished by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.British Journal of Dermatology (2021)2 Research letter

The use of hydroxychloroquine as a systemic treatment in erosive lichen planus of the vulva and vagina

ARTS repository - University of Groningen

Dissertations of the University of Groningen

   University of GroningenThe use of hydroxychloroquine as a systemic treatment in erosive lichen planus of the vulvaand vaginaVermeer, H A B; Rashid, H; Esajas, M D; Oldhoff, J M; Horváth, BPublished in:The British journal of dermatologyDOI:10.1111/bjd.19870IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Vermeer, H. A. B., Rashid, H., Esajas, M. D., Oldhoff, J. M., & Horváth, B. (2021). The use ofhydroxychloroquine as a systemic treatment in erosive lichen planus of the vulva and vagina. The Britishjournal of dermatology. Advance online publication. https://doi.org/10.1111/bjd.19870CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Research letterThe use of hydroxychloroquine as a systemictreatment in erosive lichen planus of the vulvaand vaginaDOI: 10.1111/bjd.19870DEAR EDITOR, Erosive lichen planus affecting the vulva andvagina (ELPV) is a rare inflammatory skin disease, presentingwith painful erosions and severe scarring.1 The disease courseis persistent and often refractory to treatment: up to 45% ofpatients do not experience remission with topical treatments,and evidence for systemic treatments remains scarce.2 Hydrox-ychloroquine (HCQ) is frequently used in daily practice as afirst choice systemic therapy.3 However, little evidence isavailable on use of HCQ for ELPV.2 The aim of this study wasto analyse the effectiveness and safety of HCQ in ELPV.Adult patients diagnosed with ELPV and treated with HCQbetween 2009 and 2020 were retrospectively analysed.Patients with insufficient clinical data, or patients who made ageneral objection to the use of their data in research wereexcluded. Informed consent was not collected, because ofanonymous data processing and lack of care regimen interfer-ence. Due to this study’s noninterventional character, the Med-ical Research Involving Human Subjects Act did not apply,and official approval by the medical ethics review committeewas not required.Clinical response was analysed using the Physician’s GlobalAssessment score. Clinical response was defined as a decreasein physical signs for at least two consecutive hospital visits. Aflare-up was defined as return to baseline disease activity orworsening of physical signs after initial response. Adverseevents (AE) were graded in severity with the Common Termi-nology Criteria for Adverse Events (CTCAE).4A total of 15 patients with ELPV treated with HCQ wereanalysed. Beforehand, five patients were excluded, because ofinsufficient clinical data (n = 4, all follow-up in a differenthospital) and HCQ being used for another indication (n = 1).The median age was 55 years (range 23–82) and 67% werepostmenopausal. The median diagnostic delay was 2 years(range 0–11). Overall, 87% (n = 13) had biopsy-provenlichen planus, nine of which were based on vulval biopsy.Other biopsy sites included the oral mucosa and skin. Orallichen planus was present in 53% (n = 8).Fourteen patients used concomitant topical treatment,mainly tacrolimus 001% ointment (47%), topical steroids(67%) and hydrocortisone/estriol vaginal creams (27%). HCQwas the first systemic treatment in 11 patients, whereas fourhad received one or more immunosuppressive drugs before,which were HCQ (n = 2), prednisolone (n = 2), methotrexate(n = 1) and ciclosporin (n = 1).In this study, HCQ dosage, dependent on disease activityand tolerance, ranged between 200 and 600 mg, with oneoutlier of 800 mg in a patient who was a ‘nonresponder’. Intotal, 60% (n = 9) responded to HCQ. At 3 months, allpatients were still on HCQ, with three patients reportingimprovement. At nine months, twelve patients were still onHCQ, with eight reporting improvement. Seven (47%)patients were still successfully on HCQ at 24 months.Reported dosages at initial response were 400 mg (n = 7) and200 mg (n = 2). Further dose–response correlations could notbe evaluated because of individual dosage fluctuations. Patientsvisited with a median 3-month interval (range 06–126). Themedian time to treatment response was 5 months (range 1–185). Median treatment duration was 238 months (range41–81). Reasons for cessation included ineffectiveness(n = 6), AE (n = 1), development of malignancy (n = 1) andloss to follow-up (n = 2).Three patients (20%) experienced disease flare-ups duringtreatment. Flare-ups resolved spontaneously or after dosageincrease after a median of 11 weeks (range 28–313). Eightpatients (53%) experienced AEs during treatment, most com-monly infections and gastrointestinal complaints. AEs resolvedafter dosage lowering or additional treatment (Table 1).Previous research has shown that ELPV is a difficult to treatcondition.2,3 This study suggests that HCQ can be an effectivetreatment in ELPV. Overall, 60% of the patients responded toHCQ, with almost half experiencing a long-term effect. AEs(53%) were mostly mild or moderate. Flare-ups (20%)resolved either after dosage increase or spontaneously.Our response rate to HCQ was higher compared with the36% success rate of a case audit review in ELPV.3 Unfortu-nately, no dosages were described, making comparison diffi-cult. Recently, Cline et al. reported a clinical improvement of70% with methotrexate in ELPV,5 exceeding our response rate.However, HCQ was better tolerated: only one patient stoppedbecause of an AE, compared with 30% from methotrexate use.Our results suggest that HCQ has a slow onset of action, asonly 20% reported improvement at 3 months, but 53% hadresponded at 9 months. The time taken to respond may beoverestimated, as data were collected retrospectively duringhospital visits.Limitations include the retrospective nature, the limitedheterogeneous sample size and use of concomitant topicalmedication.© 2021 The Authors. British Journal of Dermatologypublished by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.British Journal of Dermatology (2021) 1This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use,distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Although evidence about systemic treatment in ELPV isscarce, this study provides a broad view on treatment charac-teristics and safety of HCQ in ELPV in a daily care setting.2We conclude that HCQ can be an effective and safe treatmentin ELPV. Future studies are needed to further assess effectivesystemic treatments for ELPV.H. A. B. Vermeer iD ,1 H. Rashid,1 M. D. Esajas,2J. M. Oldhoff iD 1 and B. Horvath iD 11Department of Dermatology; and 2Department of Obstetrics andGynaecology, University Medical Centre Groningen, University of Groningen,Groningen, the NetherlandsCorrespondence: Marja Oldhoff.Email: j.m.oldhoff@umcg.nlReferences1 Lewis FM, Bogliatto F. Erosive vulval lichen planus – a diagnosisnot to be missed: a clinical review. Eur J Obstet Gynecol Reprod Biol2013; 171:214–9.2 Dunaway S, Tyler K, Kaffenberger J. Update on treatments for ero-sive vulvovaginal lichen planus. Int J Dermatol 2020; 59:297–302.3 Simpson RC, Littlewood SM, Cooper SM et al. Real-life experienceof managing vulval erosive lichen planus: a case-based review andU.K. multicentre case note audit. Br J Dermatol 2012; 167:85–91.4 U.S. Department of Health and Human services. Common Termi-nology Criteria for Adverse Events v4.0. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf (last accessed 8 March 2021).5 Cline A, Cuellar-Barboza A, Jorizzo JL, Pichardo RO. Methotrexatefor the treatment of recalcitrant erosive lichen planus of the vulva.JAMA Dermatol 2020; 2:2019–21.Funding sources: none.Conflicts of interest: B.H. reports fees from Janssen-Cilag (AdvisoryBoards, Educational grants, Consultations, Investigator Initiative Stud-ies), AbbVie (Advisory Boards, Educational grants, Consultations,Investigator Initiative Studies), Novartis Pharma (Advisory Boards,Consultations, Investigator Initiative Studies), UCB Pharma (AdvisoryBoards, Consultations), Leo Pharma (Consultations), Solenne B.V.(Investigator Initiative Studies), Celgene (Consultations, InvestigatorInitiative Studies), Akari therapeutics (Consultations, Investigator Ini-tiative Studies), Philips (Consultation), Roche (Consultation), Regen-eron (Consultation) and Sanofi (Consultation); fees were paid to theinstitution.Table 1 Treatment characteristics of 15 patients with erosive lichenplanus affecting the vulva and vaginaTreatment characteristics (n = 15) ValuesDosage in mg/day, range 200–800HCQ duration in months, median (range) 238 (41–81)Total follow-up duration in months,median (range)38 (4–123)Time until response in months, median(range)5 (1–185)Responders 9 (60)3 months 3 (20)9 months 8 (53)12 months 7 (47)24 months 7 (47)Patients with flare-ups 3 (20)Flare-up duration in weeks, median(range)11 (28–313)Concomitant topical anti-inflammatorytreatment14 (93)Topical corticosteroids 10 (67)HCA 25%/estriol vaginal cream 4 (27)Topical tacrolimus 0,1% ointment 7 (47)Intralesional steroid injections 1 (7)Experienced AE 8 (53)Hearing loss (CTCAE 3) 1 (7)Nausea (with weight loss) (CTCAE 2) 1 (7)Infection (CTCAE 2) 3 (20)Blurry vision (CTCAE 2) 1 (7)Gastrointestinal disturbances (CTCAE 1) 3 (20)Dizziness (CTCAE 1) 3 (20)Infections (CTCAE 1) 2 (13)Headache (CTCAE 1) 2 (13)Fatigue (CTCAE 1) 1 (7)Heart palpitations (CTCAE 1) 1 (7)Hair loss (CTCAE 1) 1 (7)Tinnitus (CTCAE 1) 1 (7)General malaise (CTCAE 1) 1 (7)Data are n (%) unless otherwise specified. AE adverse event;CTCAE, Common Terminology Criteria for Adverse Events(CTCAE grade 1–5: mild, moderate, severe, life-threatening,death); HCA, hydrocortisone; HCQ hydroxychloroquine.© 2021 The Authors. British Journal of Dermatologypublished by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.British Journal of Dermatology (2021)2 Research letter

Proceedings - University of Groningen

Erosive lichen planus affecting the vulva and vagina (ELPV) is a rare inflammatory skin disease, presenting with painful erosions and severe scarring.1 The disease course is persistent and often refractory to treatment: up to 45% patients do not experience remission with topical treatments, while evidence for systemic treatments remains scarce.2 Hydroxychloroquine (HCQ) is frequently used in daily practice as a first choice systemic therapy.3 However, little evidence is available on HCQ for ELPV.2 The aim of this study was to analyse the effectiveness and safety of HCQ in ELPV

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The use of hydroxychloroquine as a systemic treatment in erosive lichen planus of the vulva and vagina

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