Vulvar lichen planus–induced vulvovaginal stenosis: A case report and review of the literature

Abstract

The authors report a case of vulvar lichen planus–induced vulvovaginal stenosis along with a review of the current literature. The authors outline a case of a patient with biopsy-proven vulvar lichen planus who subsequently developed a vulvovaginal stenosis. Treatment was initiated with clobetasol ointment, oral prednisone, later transitioned to oral methotrexate and clobetasol, and then switched to acitretin. Collaboration with the patient’s family physician and the hypertension clinic has been sought to remove medications associated with lichenoid reactions from the patient’s regimen. Review of literature was conducted through Ovid MEDLINE. Only six cases of vulvar lichen planus–induced vulvovaginal stenosis had been found, suggesting the relative rarity of this severe disease presentation. The patient has achieved control with her current regimen, as well as some clinical improvement of the resulting vaginal stenosis. Vulvovaginal stenosis can be induced by vulvar lichen planus, and its management requires a multimodal and multidisciplinary approach.

Introduction

Vulvar lichen planus (VLP) is a disease of the middle-aged female population with an association to oral manifestations, where 19%–67% of women affected by oral lesions have concomitant vulvovaginal presentations.¹

The most common manifestation, erosive atrophy, can progress to loss of the labia minora and clitoral hood, desquamative vaginitis, and vaginal stenosis.^1,2 Oral lichen planus (LP) may also present with desquamative gingivitis, and vulvovaginal gingival (VVG) syndrome is desquamative gingivitis associating with vulval and vaginal desquamation.^3,4

To our knowledge, 23 reports have been published regarding LP-induced vulvovaginal stenosis,^2,5–13 most recently in 2013 by Singh et al.⁹ who commented on the rarity of vulvovaginal stenosis progressing from isolated VLP, a separation from VVG syndrome.⁹

A search via Ovid MEDLINE identified 23 patients with LP-induced vulvovaginal stenosis. From these patients, six were determined to exclude gingival involvement, suggesting the rarity of isolated VLP-induced vulvovaginal stenosis (Table 1). The authors outline a case of a patient with biopsy-proven VLP who subsequently developed a vulvovaginal stenosis. Verbal and written patient consent were obtained for publication.

Table 1.

Summary of case reports describing LP-induced vulvovaginal stenosis.

Report	Patient (years)	Vulvar symptoms	Vulvar exam findings	Extra-genital sites	Biopsy	Treatment
Soper et al.8	50	Bloody vaginal discharge and adhesions	Atrophic vagina with stenotic apex; erythematous, friable vestibule, and vagina	Buccal mucosa, nails	Vestibule: LP	- Steroids - Retinoic acid derivative
	55	Severe dyspareunia	Atrophic vulva and vagina; vaginal stenosis	Buccal mucosa	Vestibule: LP	- Systemic steroids - Vaginal dilatation
Edwards2	66	Not described	Erythema; agglutination of labia minora, frenulum, and clitoral hood	Buccal mucosa, gingiva	Not described	- Oral dapsone - Griseofulvin - Isotretinoin
	63	Not described	Erythema of vulva; complete agglutination of labia minora, clitoral hood, and anterior commissure with erosion	Buccal mucosa, gingiva	Not described	- Mid-potency topical corticosteroids - Oral griseofulvin
Bermejo et al.13	63	Vulvar burning; dyspareunia	Atrophic vulva; erosive vaginitis; vaginal stenosis	Gingiva, buccal mucosa	Buccal mucosa: irregular acanthosis and liquefaction degeneration of the stratum germinativum	Not discussed
	65	Pruritus, discomfort in external genitalia; dysuria	Elephantiasis of labia majora; desquamative vulvitis; atrophic synechial vaginitis	Buccal/palatal mucosa	Buccal mucosa: epithelial atrophy, hydropic degeneration of basal layer, and band-like mononuclear infiltrate
	54	Genital pruritus; dyspareunia	Vestibular and vaginal erosions; vaginal stenosis	Buccal mucosa, tongue	Buccal mucosa: flattened epithelium, liquefaction of basal layer, and lymphocytic infiltrate
	44	Genital erythema and discomfort; dyspareunia	White lichenoid striations on vestibule; vaginal stenosis; erosions at fourchette	Buccal mucosa, gingiva	Vulvar: chronic inflammatory infiltrate Margins of vulvar ulcer: hyperkeratotic epithelium, band-like infiltrate
Walsh et al.12	36	Pain; bleeding; prohibition of sexual intercourse; recalcitrant to treatment	Vaginal stenosis; erythema to vulvar vestibule and vagina; anterior labial minora fusion	Gingival, buccal mucosa	Biopsy proven (exact sites not described)	- Vaginal and oral prosthesis for steroid application - Iontophoresis
Jones et al.7	62	Dyspareunia × 40 years; sexual intercourse became impossible by age 50	Raised tumor on right anterior vulva; loss of labia minora; buried clitoris; vaginal stenosis and adhesions	Cutaneous, ocular, auditory, oral, pharyngeal	LP (site of original diagnosing biopsy not stated)	- Patient presented with further vulval tumors treated with excision, intralesional triamcinolone acetonide and oral cyclosporin
Lotery and Galask11	55	Introital dyspareunia; bleeding; vulvar burning and itching; difficulty with intercourse	Hyperkeratosis to right labium minus; erosions to vulvar vestibule and vagina; vaginal stenosis	Buccal mucosa	None	Tacrolimus 0.1% ointment, dilatation with vaginal dilator coated in estrogen vaginal cream
	55	Progressive vaginal narrowing; intermittent burning and itching of vaginal introitus	Vulvar vestibular and vaginal erosions; Wickham striae on surrounding vulvar skin; partial involution of labia minora, phimosis of clitoral hood; vaginal stenosis	Oral (buccal mucosa and gingival) and cutaneous	None
	49	Introital dyspareunia; burning; itching; soreness	Erosion of vulvar vestibule; vaginal stenosis	None	None by authors
Byrd et al.6	53	Genital pain	Introital, labial erosions, stenosis	Oral, gingival, otic	Vaginal: LP	Topical tacrolimus 0.1% ointment twice a day to affected areas
	67	Genital pain; soreness; burning	Introital, labial erosions, stenosis, labia destroyed	Oral, gingival, cutaneous	Vulvar: LP
	67	Genital pain	Introital, labial erosions, stenosis, labia destroyed	Oral, gingival, cutaneous, otic, esophageal	Esophageal: LP
Kortekangas-Savolainen and Kiilholma5	65	Soreness of outer genitalia	Vulval and vaginal strictures × 7 years	Cutaneous	Cutaneous: LP Vaginal mucosa: non-specific	- History of surgical vaginal dilations - Oral methotrexate 7.5 mg weekly, digital dilatation followed by tacrolimus cream with local estrogen - Vaginal dilatation - Oral methotrexate 7.5 mg weekly - Ultrapotent steroid cream - Local estrogen - Vaginal/ urethral/urinary bladder dilations - Methotrexate 7.5 mg weekly - Tacrolimus cream
	64	Dyspareunia	Ulceration to orifice of vagina and vulva; vaginal stenosis	Oral (not specified if gingival)	Vulvar: both LS and LP
	45	Not described	Ulcerations in vulvar mucosa; vaginal and urethral stricturing	Scalp Oral (not specified if gingival)	Oral: lichenoid reaction Vulvar: not informative
	56	Not described	Erythema and ulceration to external genitalia; stenosis of vagina and urethra	None	Bladder: cystitis Vulvar/vaginal: non-specific	- Vaginal, urethral, bladder dilations - Methotrexate 7.5 mg weekly - Ultrapotent corticosteroid cream followed by 0.1% tacrolimus ointment - Local estrogen
	58	Bleeding of vaginal mucosa; dyspareunia	Vaginal stenosis	Oral (not specified if gingival)	Vaginal: LP	- Vaginal dilatation - Local potent corticosteroid and tacrolimus - Oral methotrexate 7.5 mg weekly - Local estrogen cream
Jang and Fischer10	55	Recurrent vulvar pruritus × 25 years; introital dyspareunia	Vulvovaginal erythema and erosions + labial fusion	None	Vulvar/vaginal introitus: inflammatory change confirming LP	- Complicated treatment course - Ultimately, oral methotrexate 7.5 mg weekly + clobetasol dipropionate 0.05% ointment - Clobetasol ointment was switched to tacrolimus 0.03% ointment once daily
Singh et al.9	50	Genital pruritus and erosions	Fusion of labia minora; stenosis; ulcerated violaceous plaques	Left buccal mucosa, left infra-mammary region	Vulvar: epidermal basal cell degeneration with a band-like infiltrate of lymphocytes in upper dermis	- Oral prednisolone tapered from 40 mg daily - Clobetasol propionate 0.05% cream - Oral antihistamines

LP: lichen planus; LS: lichen sclerosus.

Case report

A 56-year-old female patient presented with a 16-month history of vulvar irritation with itching and pain, as well as vaginal burning. She presented with dyspareunia, which limited her once regular sexual activity. Six months prior to presentation to clinic, intercourse had become too painful, and vaginal penetration could not be attained.

Her medical history included hypertension, gastroesophageal reflux disease, arthritis, two vaginal births, a tubal ligation, and a hysterectomy for abnormal uterine bleeding. She was post-menopausal and was initially started on oral Premarin, later switched to a transdermal patch and topical estrogen added by gynecology. Her other medications included diclofenac/misoprostol, perindopril, hydrochlorothiazide, pantoprazole, candesartan, and atenolol.

Her initial gynecologist for dyspareunia noted narrowing and shortness of the vagina, primarily at the vaginal vault, attributed to atrophic menopausal change and previous hysterectomy. She subsequently saw a dermatologist who biopsied the mucosal lesions and diagnosed LP. The condition worsened and was unresponsive to local therapy, precipitating referral to the multidisciplinary vulvar clinic with a dermatologist and gynecologist present concurrently. When seen at our clinic, a speculum or even a small finger could not be inserted due to a complete blockage just inside the introitus. No pelvic mass was palpated on examination. There were large erosions on the inner aspects of the labia and the introital area. In the oral mucosa, superficial erosions with Wickham striae characteristic of LP were noted on the lateral aspect of the tongue.

Vulvar biopsies showed a lichenoid reaction consistent with LP. As eosinophils were present, a lichenoid drug eruption was considered. Hepatitis C serology was negative.

Vulvar erosions (Figure 1) improved with oral prednisone 30 mg daily, topical clobetasol ointment twice daily, and triamcinolone acetonide paste was also prescribed for the oral erosions. The patient was then tapered off prednisone and started on oral methotrexate (5–20 mg/week). Methotrexate in combination with continued topical corticosteroid led to further re-epithelialization, and the use of a vaginal dilator was suggested for the introital opening. However, after over 3 years of therapy with methotrexate which improved symptoms of pain, burning, itching, and vulvar erosions, the patient’s disease became recalcitrant to methotrexate, and she was switched to acitretin. It is noted that the patient remained on atenolol and hydrochlorothiazide as per her cardiologist during this time.

Figure 1.

Erythema with an erosion in the inferior vaginal introitus as well as vaginal stenosis.

During this period, a brief trial of topical tacrolimus was attempted but discontinued due to pruritus and irritation. At the 3-year follow-up, acitretin (25 mg/day) was started. The patient achieved some symptom control of her vulvar pain and some re-epithelialization as she continued along with two additional tapering courses of prednisone and clobetasol ointment.

The patient’s vulvar LP remitted, and her vaginal stenosis improved, after a switch of her anti-hypertensive medicine to amiloride, but unfortunately recurred when metoprolol was prescribed for her atrial fibrillation. Metoprolol is a medication associated with LP. This flare was treated with a tapering course of prednisone, clobetasol ointment on the affected vulvar areas, and 25 mg hydrocortisone suppository. Simultaneously, the patient was advised to continue calcium and vitamin D supplements, and a bone densitometry was obtained for chronic steroid use. The patient initially declined the use of vaginal dilators and now uses these irregularly. The patient continues to decline surgical release for penetrative intercourse and is content with her current clinical presentation.

Discussion

VLP-induced vulvovaginal stenosis is a debilitating condition that significantly affects a patient’s quality of life and requires a multidisciplinary approach to treatment. The pathogenesis of LP has not been conclusively proven. An autoimmune etiology is likely, involving basal keratinocyte damage by T-cells.¹ There have been speculations regarding the role of genetics through HLA-DR1 typing studies.¹⁴ Past publications have indicated associations with hepatitis C and systemic medications, including glimepiride, carbamazepine, methyldopa, and diuretics such as hydrochlorothiazide, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors, and beta-blockers.^1,15–18

There are limited published data on therapies for this condition; current available regimens do not have large-scale studies to prove efficacy and despite treatment, recurrence rates remain high.¹⁹ Initial treatment of VLP consists of ultrapotent topical corticosteroids such as clobetasol propionate and betamethasone dipropionate, with addition of calcineurin inhibitors, systemic corticosteroids, methotrexate, and retinoids with increased severity.^1,4,10 Although topical tacrolimus applications have been reported to show favorable response in resolution of the VLP in many patients,^{1,4,6,10,11,19} monotherapy could be ineffective, or even adversely affecting some patients.^1,6 Unfortunately, the treatment course of recalcitrant disease can be complicated and may require multiple modalities of treatment to resolve symptoms and signs of active disease.¹⁹ Systemic immunosuppressions, such as prednisone, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, adalimumab, and tildrakizumab, were reported to be more effective in combating VLP in combination with topical corticosteroids or tacrolimus.^{4,5,6,9,20–22} Other drugs, such as cyclosporine, were also used but with less success and more adverse effect on patients.^5,6 The efficacy of using oral prednisone alone and with topical corticosteroids to achieve initial control has been shown with eventual transition to topical tacrolimus to maintain remaining disease activity.⁶ For recurrent disease requiring systemic control, weekly methotrexate has been used.¹⁹

Singh et al.⁹ commented on the importance of multidisciplinary involvement. This is consistent with our approach, where gynecology has been integrated from the outset. Surgical treatment has been shown to address vulvovaginal agglutination, stenosis, and other severe vaginal scarring despite treatments of systemic immunosuppression,²³ sometimes leading to improved intercourse and decreased urinary symptoms. However, surgical therapy is sometimes rejected by patients as post-procedure treatments in many cases require ongoing self-management with dilators, local estrogen, and vaginal moisturizers, on a consistent basis which is often difficult to maintain. Patency, especially if the disease remains somewhat active, can be unattainable.^{4,5,9,10,24,25}

Given that drug-induced LP is a common cause of recalcitrant disease, a drug review to screen for possible drug culprits and either discontinue or switch the class of medication is part of the treatment strategy.^1,15–18 With the involvement of the patient’s family physician, the patient has discontinued her diclofenac/misoprostol use. As the patient was on multiple blood pressure medications that could exacerbate LP, a referral to the hypertension clinic was made. However, after a failed trial to discontinue atenolol, patient remains on atenolol in addition to hydrochlorothiazide and candesartan. Ongoing collaboration with the patient’s family physician and the hypertension clinic continues to explore strategies to further reduce the risk of medication-induced lichenoid reactions. Vulvovaginal stenosis can be induced by VLP, and its management requires a multimodal and multidisciplinary approach.