Vulvar Lichen Sclerosus: A Literature Review with Consideration of Integrative Therapies

Abstract

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin condition characterized by vulvar pruritus, pain, dyspareunia, and architectural changes, including significant and permanent scarring and deformity of the vulva if left untreated. Untreated VLS significantly increases the risk of invasive squamous cell carcinoma, even in asymptomatic patients. However, there is an overall paucity of preclinical and clinical research on VLS. Although the disease is becoming more commonly recognized, it is often under- or misdiagnosed and its prevalence is likely underestimated. While the exact underlying etiology is still unknown, VLS is most likely an autoimmune disorder within the background of genetic predisposition and environmental triggers. The skin and gut microbiomes also appear to be involved. The first line treatment for VLS, ultrapotent topical corticosteroids, helps relieve symptoms and reduce the risk of architectural changes and vulvar cancer. The second-line medications and treatments with more limited evidence of efficacy include topical calcineurin inhibitors, topical hormones, platelet-rich plasma, and fractional CO₂ laser therapy. Surgical intervention may also be required. Additionally, some VLS patients and practitioners report improvements with diet and lifestyle changes, nutritional supplements, low-dose naltrexone, botanical medicines, and other integrative treatments, although clinical research on these integrative therapies for VLS is generally lacking. This review aims to describe VLS in adult women, summarize the recently published literature, and provide a clinical overview that includes evidence-based integrative therapies.

Introduction

Vulvar lichen sclerosus (VLS) is a chronic, remitting, and relapsing inflammatory skin disease of the anogenital area that leads to fibrosis and progressive scarring. VLS can cause irreversible architectural changes, including fusion or loss of the labia minora, narrowing of the vaginal introitus, and sealing of the clitoral hood. It is generally characterized by intense vulvar pruritus, pain, and dyspareunia caused by tearing, erosions, and fissures, although architectural changes may occur even without symptoms.¹ If untreated, VLS significantly increases the risk of invasive squamous cell carcinoma, even in asymptomatic patients.^2–4 While the exact underlying etiology is still unknown, VLS is most likely an autoimmune disorder within the background of genetic predisposition and environmental triggers.⁵ The skin and gut microbiota also appear to be involved.⁶

The prevalence of VLS is unknown and likely underestimated since VLS often goes unrecognized and underdiagnosed.⁷ Prevalence was found to be as high as 1.7% within a general gynecology practice; whereas the prevalence in the general US population was 0.05%.^7,8 Incidence doubled between 1991 and 2011 in a large cohort study.⁹ Furthermore, while VLS has predominantly been considered bi-modal in terms of age of onset, with the highest occurrence rates in prepubertal and postmenopausal women, it can develop at any age and recent studies have found that more than half of women with VLS experience symptoms before the age of 50 years.¹⁰

The first line treatment for VLS is ultrapotent topical corticosteroids, which help relieve symptoms and reduce the risk of architectural changes and vulvar cancer when used regularly.^1,11–13 The second-line treatments include topical calcineurin inhibitors, topical hormones, platelet-rich plasma, and fractional CO₂ laser therapy, although evidence of their efficacy is more limited.^11,12,14 Surgical intervention may also be required. Additionally, some patients and practitioners report improvements with diet and lifestyle changes, nutritional supplements, botanical medicines, and other integrative treatments, although clinical research on their efficacy is limited.

Overall, there is a paucity of research on VLS. While the disease is commonly recognized, women often suffer for years before getting an accurate diagnosis and appropriate treatment. There is a growing need not only for more research but also for early and accurate diagnosis, appropriate referrals, and improved patient education. This review aims to describe VLS and provide a summary of the recently published literature on its etiology and treatment strategies. A brief discussion of diet, lifestyle, and integrative therapies is also provided.

Etiology And Pathogenesis

The etiology and precise pathogenesis of VLS are still not fully elucidated. Evidence suggests VLS is an autoimmune disease triggered by environmental factors in genetically predisposed women.^5,15 Evidence for autoimmunity includes the higher rates among twins and family members, the significant positive association with particular human leukocyte antigen (HLA) genes and haplotypes, and the strong, positive correlation with co-existing autoimmune diseases, particularly autoimmune thyroid disease (Hashimoto’s thyroiditis and Graves’ disease), alopecia areata, vitiligo, and pernicious anemia.^16–21 In three studied cohorts of women with VLS, autoimmune thyroid disease occurred in 12-30% of patients.^18,19,21 Women with VLS have an increased incidence of circulating autoantibodies such as anti-thyroid and anti-nuclear antibodies.¹⁹

Interactions between three processes appear crucial in VLS pathogenesis: autoimmune mechanisms; disruption of fibroblast and collagen homeostasis; and oxidative stress.^15,22 Although they do not comprehensively explain pathogenesis, autoantibodies to extracellular matrix protein 1 (ECM1), an essential scaffolding glycoprotein critical to dermal equilibrium, have been found in some women with VLS.²³ ECM1 antibodies may play a role in the augmented collagen synthesis and fibroblast proliferation that characterize VSL pathogenesis.⁵ The disruption of collagen and fibroblast homeostasis is characterized by T cell (Th1) infiltration in the dermis.⁵ In this Th1-mediated chronic inflammatory state, genes involved in T cell inhibition are downregulated, and inflammatory cytokines, such as TNF-alpha and IL-6, are increased.^5,15,24 The subsequent inflammation is hypothesized to induce oxidative stress, injuring tissues and microvessels, and activating signaling pathways involved in fibroblast and collagen metabolism. This culminatesin dysregulation of pro- and anti-fibrotic mechanisms, dermal fibrosis, and the distinctive histopathological features of VLS.⁵

Oxidative stress, in addition to its involvement in the pathogenesis of VLS, is also theorized to be a cause of its progression to vulvar cancer and its VLS-associated precursor, differentiated vulvar intraepithelial neoplasia (dVIN). Oxidative stress biomarkers in VLS lesions progressively increase from normal tissue to dVIN to invasive cancer.²⁵ Inflammatory damage and poor oxygenation of thickened, sclerotic tissue causes an ischemic stress response that can lead to both genetic and epigenetic changes that facilitate cancer progression.^22,26,27 Hypermethylation of promoter regions and tumor suppressor genes, along with mutations in the crucial tumor suppressor gene, TP53, have been found to distinguish between VLS lesions that progress to cancer from those that do not.²⁶ Increased methylation leads to inhibition of the binding of regulatory proteins and disruption of important cellular processes like DNA repair, cell cycle control, and apoptosis, while TP53 mutations lead directly to the loss of tumor suppressor function.

Recent evidence also points to the involvement of the skin and gut microbiota in the etiology of VLS. Significant differences in vulvar skin, vaginal, and gut microbiota species and diversity have been found in VLS patients compared to healthy controls.^6,28–30 The vaginal microbiome in postmenopausal VLS patients in one study was dominated by possibly harmful bacteria including Streptococcus anginosus, Gardnerella vaginalis, or Lactobacillus iners, potentially inducing damage by negatively altering extracellular matrix proteins and defensins, breaking down the vaginal mucus layer and epithelium, or inducing pro-inflammatory cytokines.⁶ In another study, the vulvar skin microbiota in menopausal women with VLS had fewer overall Lactobacillus species and a relative abundance of Prevotella and other harmful anaerobic species, in contrast to asymptomatic controls.²⁸ Differences have also been found in the urinary and lower vaginal microbiota, with increased relative abundance of Streptococcus compared to controls.³⁰

In the gut, significant differences have been found in the relative abundance of the species Eubacterium coprostanoligenes and phylum Euryarchaeota in VLS patients compared to controls.³⁰ The fact that Euryarchaeota is also increased in patients with rheumatoid arthritis and multiple sclerosis suggests an inflammatory role.³⁰ A study in girls with VLS found a higher relative abundance of Dialister species in the gut, also consistent with inflammatory diseases.²⁹ They also had a lower relative abundance of Roseburia faecis, commensal producers of short-chain fatty acids, including butyrate, known to control inflammation and beneficially affect the systemic immune system.²⁹

In addition to the etiological factors described above, limited evidence exists for the role of hormonal influences, infections, trauma, and chronic irritation as possible causal or triggering agents in VLS.^5,31 The higher incidence of VLS in peri- and post-menopausal women suggests a pathogenic role of sex hormones, although there is scant evidence for their etiological role.⁵ Infections (Borrelia burgdorferi and Epstein Barr virus) and microtrauma have also been considered in the etiology of VLS, but again, the evidence is not robust.³¹ The controversial results related to these potential etiological agents are likely explained by the complex, multifactorial process of VLS pathogenesis.

Presentation

Intense vulvar pruritis is the most common presenting VLS symptom.¹ Sexual pain and dysfunction occur in nearly 60% of patients, particularly premenopausal women, and include dyspareunia, tearing with intercourse, and decreased clitoral sensation.^32,33 Painful fissures often occur during vaginal insertion. Erosions and fissures commonly occur between the clitoris and urethra, in the interlabial sulci, and at the base of the posterior fourchette. These lesions, as well as the scarring and atrophic changes, can also cause intense pain, stinging, burning, impeded urinary flow, and problems with defecation when the perianal area is involved. Varying periods of remission interspersed with recurrent flares are common. In up to one-third of patients, VLS may be asymptomatic, with an incidental diagnosis on examination, even when the disease shows advanced architectural changes.⁸

VLS significantly increases the risk of invasive squamous cell carcinoma and its precursor, vulvar intraepithelial neoplasia, especially when left untreated.^3,4,9,34 The risk of increased incidence of vulvar cancer in women with VLS during their lifetime is unknown and may be anywhere between 3.5% to 7%.^13,35 About 60% of vulvar squamous cell carcinoma cases have a background of VLS.¹³ Vulvar squamous cell carcinoma may appear as nodules, persistent fissures, hyperkeratotic plaques, and non-healing ulcers.

VLS is significantly associated with depression and anxiety and has a significant negative impact on well-being and quality of life (QoL).^36,37 Women with VLS have a 2.16- and 2.5-fold higher risk of comorbid depression or anxiety, respectively.³⁶ Contributing factors include its annoying and painful symptoms, chronicity, diminished ability to perform activities of daily living, sexual dysfunction, disfiguring anatomical changes, partial and temporary treatment response, and cancer risk.^33,38 Compared to untreated VLS patients, those treated for the long-term have significantly better Vulvar QoL Index scores on all measures, including overall QoL, anxiety, symptoms, activities of daily living, and sexuality.³⁹ Only a minority of patients treated long-term report ongoing poor QoL, mainly due to sexual symptoms and anxiety.³⁹

Examination and Diagnosis

On examination, lesions appear as flat, ivory, or porcelain spots which may coalesce into pale, crinkly, thin patches, and plaques. Erythema, ecchymosis, and itching-related excoriations may be observed and, occasionally, hyperkeratosis is prominent. The sites most characteristically involved are the interlabial sulci, labia minora and labia majora, clitoris, and clitoral hood. Since VLS is a scarring dermatosis, it may cause resorption of the labia minora, sealing of the clitoral hood, and covering of the clitoris. The entire vulva may be involved, with possible extension to the perineum and perianus, giving rise to the characteristic ‘figure eight’ shape.¹² The genitocrural folds, buttocks, and thighs may be affected as well. The vagina and cervix are usually spared. Differential diagnoses include lichen planus, dermatitis, or lichen simplex chronicus.

VLS is diagnosed clinically and does not always require a confirmatory biopsy, according to existing clinical guidelines.^11–14 Biopsies can be unreliable, with missing or nonspecific histological findings.^40,41 Biopsies can be reserved for situations in which the clinical diagnosis is uncertain, first-line treatment fails after appropriate treatment duration, or malignancy is suspected.¹¹

Delayed diagnosis is common even though early, prompt diagnosis and treatment of VLS may revert skin changes and prevent scarring and cancer development.² A study in reproductive-aged VLS patients found one-third were incorrectly diagnosed and treated for recurrent candidiasis and estrogen deficiency.¹⁰ To provide timely and accurate diagnosis, healthcare providers must consider VLS as a possible diagnosis in patients presenting with vulval symptoms. They should perform examinations, know what to look for, and provide appropriate referrals in uncertain cases.⁴²

Treatment

No known curative VLS therapies currently exist. Treatment goals are to alleviate symptoms, prevent or possibly reverse architectural changes, minimize the risk of vulvar cancer, and prevent or improve sexual dysfunction. Only a minority of patients achieve complete resolution of symptoms.⁴³ Clinical guidelines recommend treatment for all women with VLS, even when asymptomatic, given the progressive course and heightened cancer risk.¹³ Treatment should be maintained for life to decrease the frequency of recurrences and “flares”, which are common, prevent architectural changes and scarring, and decrease the risk of cancer. Owing to the seriousness of the risk, healthcare practitioners must ensure patients are educated, know what to look for, and have regular follow-ups.

Corticosteroids

Potent and ultrapotent topical corticosteroids are the standard first-line treatment for VLS, given the strong evidence that they control symptoms and reverse clinical and histopathological changes.⁴⁴ Use of clobetasol propionate 0.05% ointment, the most extensively studied and commonly prescribed of these, mometasone furoate 0.1%, or other topical corticosteroids of similarly high potency, is supported by expert guidelines.^11–14 Ointments are recommended over creams. A commonly recommended dosing regimen for clobetasol propionate 0.05% ointment is a large pea-sized amount (0.33 grams) to a half-fingertip unit (0.5 g) applied to the vulva and/or perianal areas once daily for 4 weeks, then every other day for 4 weeks, then twice weekly indefinitely for maintenance purposes. For women not responding to topical steroid therapy, intralesional steroid injections (triamcinolone 3.3-10 mg/ml) may be used.¹¹

Existing guidelines differ in their recommendations for long-term maintenance aimed at preventing recurrences and malignancy.^1,12,14 European guidelines recommend twice-weekly clobetasol propionate 0.05% or mometasone furoate 0.1% ointment, noting their effectiveness and safety in maintaining remission and helping to prevent malignancy.¹⁴ The American College of Obstetricians and Gynecologists (ACOG) guidelines call for individualized corticosteroid therapy titrated to the lowest dose possible to maintain symptom resolution.¹² Patients with VLS who adhere to topical steroid treatment have a reduced risk of recurrence of vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.¹ The risk of vulvar carcinoma is significantly lower in treatment-compliant patients who maintain normal skin color and texture with long-term individualized topical corticosteroid treatment, but not in partially-compliant patients or those who use treatment only as needed to control symptoms.^2,45

Concerns about skin atrophy, secondary infections, and risk of systemic absorption with long-term corticosteroid use are addressed in guidelines and by clinical experts.^1,11,12,46 Long-term maintenance with high-potency topical corticosteroids twice weekly is considered safe.¹¹ The ACOG guidelines note that long-term maintenance therapy does not appear to lead to atrophy, telangiectasia, striae, or secondary infection, while the International and European guidelines recommend not more than one 30-gram tube of strong steroids should be used in three months to avoid skin thinning.^11,12,14 Potent steroids applied to the labia in VLS patients have not been shown to cause atrophic changes, clinically or histologically.⁴⁶ Furthermore, systemic absorption appears to be minimal and is not generally considered a safety concern.^2,46 In patients treated with clobetasol propionate 0.05% daily for three months, then three times weekly until complete remission or two times monthly if treatment continued longer than 12 months, no systemic or local atrophic effects were noted within the median follow-up of 4.7 years.⁴⁵ Another study in VLS patients treated with twice-daily clobetasol propionate 0.05% for 22 months found no histologic evidence of infection or skin atrophy.⁴⁷ If corticosteroids do cause vulvar redness, burning, or fragility, researchers have noted a quick reversal of symptoms once potency is adjusted.¹

Topical calcineurin inhibitors

Immunosuppressive topical calcineurin inhibitors (tacrolimus and pimecrolimus), which inhibit the activation of T cells, are also used as VLS treatments and, although effective in clinical trials, are generally recommended only as second-line treatments.^{1,11,13,48,49} Studies comparing topical tacrolimus and pimecrolimus to potent topical corticosteroids for up to 18 months have found that the former is not as effective and safe as VLS treatments, allowing for theoretical risk of malignant transformation due to their localized immunosuppressive action.^48,50 In addition, they are also more expensive and more likely to sting and burn.¹

Topical hormones

Although earlier reports showed the potential efficacy of topical progesterone, newer research does not support its use. A 2012 systematic review and meta-analysis of seven randomized trials found no evidence supporting the efficacy of progesterone, while clobetasol propionate, mometasone furoate, and pimecrolimus were efficacious.⁴⁴ More recently, a randomized double-blind trial compared 12 weeks of topical progesterone 8% ointment to topical clobetasol propionate 0.05% ointment in reducing the clinical severity of VLS.⁵¹ Progesterone was significantly inferior to clobetasol propionate in controlling clinical signs and symptoms. However, since the study did not contain a placebo arm, the efficacy of topical progesterone treatment, if any, could not be assessed.

Topical testosterone has also been used in VLS. Androgen receptors are enriched in normal vulvar skin and testosterone may have a positive trophic effect on vulvar epithelium.⁵² Furthermore, free serum testosterone and androstenedione are significantly decreased in VLS patients.^53,54 However, a year-long, double-blind, controlled study comparing topical 2% testosterone propionate with petroleum ointment found no significant difference.⁵⁵ A larger retrospective study comparing the effects of topical testosterone and clobetasol on symptoms, remission, and recurrence rates in VLS patients found that clobetasol was significantly superior to testosterone for managing both symptoms and recurrence rates.⁵⁶ Based on the results of these studies, topical testosterone has been deemed ineffective in treating VLS.¹⁴

While estrogen does not treat VLS directly and has not been studied as a VLS treatment, estrogen creams used topically and/or intravaginally can play an important role in managing VLS in postmenopausal women. Symptoms of genitourinary syndrome of menopause confound the symptoms of VLS and must be addressed concurrently. Reducing hypo-estrogenic atrophic changes with topical estrogen helps to relieve ongoing pain and itching from dryness and fragility related to the genitourinary syndrome of menopause. Low-dose estradiol (0.01%) cream can be applied to the introitus and inserted vaginally. The typical dose is 2-4 grams nightly for two weeks followed by one gram twice weekly. Case reports indicate the resolution of refractory VLS symptoms with the initiation of estradiol cream in these patients.⁵⁷

Retinoids

Topical and oral retinoids in VLS are controversial. Topical retinoids may have a beneficial effect in cases of hyperkeratotic VLS but proper studies are lacking.⁵⁸ Systemic retinoids have evidence of benefit in treatment-resistant VLS and may be considered a third-tier treatment in these cases.⁵⁸

Laser/photodynamic therapies

Fractionated carbon dioxide (CO₂) laser has emerged as a second-line VLS therapy, although its efficacy is uncertain based on mixed clinical trial results. With its superficial micro-ablative effect in soft tissues and pulsed beam to protect tissues from overheating, fractionated CO₂ laser may stimulate connective tissue remodeling and production of new collagen, fibroblasts, and ground matrix.⁵⁹ In an unblinded randomized controlled trial comparing fractionated CO₂ laser with clobetasol, more improvement occurred in the laser group, although only among women who had previously used clobetasol.⁶⁰ In another recent, double-blind, randomized trial, both sham and laser treatments resulted in statistically significant improvements in symptoms and minimal improvement in histopathology scores.⁵⁹ In a third non-randomized, unblinded study assessing fractional CO₂ laser as adjunctive treatment in patients with VLS recalcitrant to topical corticosteroids, treatment improved symptoms, predominant clinical signs, architectural changes, QoL, and sexual function, although histological scores remained unchanged.⁶¹ To date, the efficacy of fractionated CO₂ laser is uncertain and although the therapy is expensive and not covered by insurance, many patients seek it out.

Photodynamic therapy is another energy-based therapy with possible clinical benefit, especially in terms of subjective complaints related to skin lesions.⁶² The treatment uses photosensitizing chemical substances, typically 5-aminolevulinate, to cause phototoxicity. When combined with oxygen and light of an appropriate wavelength, selective photooxidation of lesional tissues occurs without damaging surrounding healthy skin. A 2021 systematic review of twenty studies found significant improvements in subjective symptoms, particularly pruritus and sexual dysfunction.⁶² There was high variability in terms of dose and intensity, however, and several studies found no significant improvement in clinical and histopathological features despite the subjective improvement. Although local anesthesia is provided, pain is the most reported side effect during and after treatment.

Platelet-rich plasma and lipofilling

Intralesional platelet-rich plasma and lipofilling (fat grafting) are newer VLS treatments already used clinically despite limited and inconsistent evidence.^63–66 Autologous platelet-rich plasma contains high levels of growth factors and other compounds that increase collagen, modulate remodeling, and thicken the epidermis.⁶⁶ Clinical trials of intralesional platelet-rich plasma have generally supported subjective improvements in symptoms and QoL in VLS patients, but not histopathologic evidence of treatment efficacy like that seen with corticosteroids.^65,66 Lipofilling, also used for VLS, can reduce skin fibrosis resulting from fibroproliferative diseases or post-traumatic scarring since adipose tissue can produce and secrete growth factors, cytokines, and other compounds with immunomodulatory, pro-angiogenic, or anti-fibrotic effects. A review of studies investigating lipofilling for VLS in 2021 found that while trials were small and did not include objective evidence of histopathologic improvement, they all demonstrated a decrease in clinical symptoms and improvement in QoL.⁶³ More recently, the combination of lipofilling and platelet-rich plasma led to both histopathologic and clinical improvements, including a significant decrease in all inflammatory cell types, as revealed by skin biopsy.⁶⁴

Surgical treatments

Vulvoperineoplasty and other surgical interventions are sometimes used for labial adhesions, introitus or urethral strictures, clitoral phimosis, or other causes of functional limitations. Perineoplasty has a high satisfaction rate in VLS patients with dyspareunia who wish to regain sexual function, although relapse and residual pain are not uncommon.⁶⁷ Surgical treatments require postoperative care regimens to maintain the restored anatomy, including continued use of potent corticosteroids, daily manual massage, and the use of vaginal dilators to separate adhesions and prevent re-adhesion.^13,68 Topical lidocaine can be used to reduce pain with dilation.

Integrative therapies for VLS

Avoidance of irritants

VLS clinical guidelines recommend avoidance of irritants and fragranced products on the affected areas, including soap (water should be used to clean the vulva).^11–13 Guidelines also suggest reducing irritation by gently patting the vulva dry after bathing; wearing 100% cotton or silk underwear and loose clothing; using 100% cotton, unscented menstrual pads or tampons; and using adequate amounts of unscented, (preferably silicone-based) lubricants during intercourse.^12,13 Since exposure of lesions to urine can irritate affected skin, avoiding toilet paper and rinsing the genitals after urination with plain water using a peri bottle, bidet, or sitz bath can also be helpful.¹²

Emollients

After initial corticosteroid treatment, regular application of a preservative-free, unscented emollient is recommended as an integral part of VLS treatment to hold moisture in the skin, preserve barrier function, and prevent fissures and flares.^11–13 Emollient barrier preparations may help relieve symptoms but do not improve the histopathological features of VLS.^12,13 Petroleum-based products such as Aquaphor are commonly recommended, although many non-petroleum barrier preparations without common irritants and allergens are also available.

Low-dose naltrexone

Although there are no clinical trials in VLS patients, data from preclinical studies, case reports, and small clinical trials indicate that both oral and topical low-dose naltrexone (LDN) could be helpful in the treatment of pruritus, wound healing, and pain in a variety of inflammatory skin diseases.^69–71 A systematic review published in JAMA Dermatology in 2019 concluded that LDN (1.5 to 4.0 mg/d) is a safe, effective treatment for benign familial pemphigus (Hailey-Hailey disease) and lichen planopilaris, as well as for pruritus associated with several other skin conditions.⁶⁹ More recent evidence suggests LDN may also effectively treat pruritus in systemic sclerosis, atopic dermatitis, and psoriasis.^72–74

While naltrexone competitively inhibits opioid receptors in high doses, LDN transiently blocks opioid receptors which prompts the upregulation of endogenous opioids and has immunomodulating effects.⁷⁵ LDN is thought to exhibit its effects on dermatologic conditions through immune/inflammation regulation and skin regeneration.⁶⁹ It is proposed that by upregulating mu-opioid receptors, binding toll-like receptor 4, and increasing endogenous endorphin production, LDN decreases inflammation and upregulates keratinocyte differentiation.⁷⁵ Topical 1% LDN creams can be compounded and have been shown to effectively deliver LDN transdermally and to decrease the inflammatory cytokine IL-6 and markers of cellular proliferation in a psoriasis tissue model.^76,77 Topical LDN was also shown to effectively treat wounds in type 1 diabetic rats, accelerating wound closure via an increase in DNA synthesis, mast cells, platelet-derived growth factor, and vascular endothelial growth factor (VEGF).⁷⁸

Vitamin E

A few randomized trials examined topical vitamin E in VLS.^79–81 In terms of its efficacy as a maintenance therapy after initial corticosteroid treatment, topical vitamin E was similar to other emollients but inferior to corticosteroids and non-steroidal topical cream.⁷⁹ In one study, daily vitamin E was compared to either daily cold cream or twice weekly mometasone furoate 0.1% ointment for 52 weeks in VLS patients who had achieved remission on initial corticosteroid treatment.⁸¹ Preliminary published results showed similar relapse rates in vitamin E and cold cream groups, whereas no relapses occurred in the corticosteroid group. Another randomized controlled trial compared a two-week application of vitamin E oil to a 2% crisaborole ointment in patients with either VLS or vulvar lichen simplex chronicus.⁸⁰ Crisaborole, a non-steroidal therapy approved by the FDA in 2018 for atopic dermatitis, is an inhibitor of boron-based phosphodiesterase (PDE4), a key regulator of inflammatory cytokine production in the skin. Crisaborole was significantly superior to vitamin E managing histopathological changes and providing symptom relief.

ASU

A small, uncontrolled study in women with VLS assessed the efficacy and tolerability of a topical cream containing avocado-soybean unsaponifiable (ASU) along with a dietary supplement containing ASU, vitamin E, and para-aminobenzoic acid.⁸² ASU is a dry extract of avocado fruit and soy germinated seeds containing phytosterols known to decrease proinflammatory mediators and, in preclinical studies, shown to improve wound healing.⁸³ It is approved adjuvant therapy for knee and hip osteoarthritis in France and for scleroderma in Italy. 23 subjects used the cream [Repasine cream; Pharmaday; Italy], which contained hyaluronic acid, vitamin E, sodium carboxymethyl beta-glucan, dimethylmethoxy chromanol, and trimethylglycine, twice daily for 24 weeks. The dietary supplement [Repasine capsules; Pharmaday], containing 300 mg ASU, vitamin E, para-aminobenzoic acid, and phytosterols, was administered for the first 12 weeks, two capsules daily between meals. Mean symptom and sign scores decreased significantly after treatment. Histopathological features were not assessed.

Probiotics

While there are still many questions about the interplay between the microbiome and VLS, restoring homeostasis in the vaginal, vulvar, and gut microbiomes with oral or vaginal probiotics may be a useful adjunctive treatment, particularly if opportunistic infections develop from corticosteroids and other treatments. Multiple meta-analyses have found probiotics effectively prevent and treat bacterial vaginosis (BV), vulvovaginal candidiasis, and other disorders of the female reproductive tract.^84,85 Oral and vaginal probiotic formulations featuring various Lactobacillus species and strains have been shown in clinical studies to significantly improve the microbial pattern in vaginal dysbiosis.⁸⁶ Oral administration of L. rhamnosus GR-1 and L. reuteri RC-14 effectively restored the vaginal flora in healthy women, women with BV, and postmenopausal women in randomized, placebo-controlled trials.^87,88 After BV treatment with metronidazole, long-term administration of either oral probiotics (L. crispatus LMG S-29995, L. brevis, and L. acidophilus) or vaginal probiotics (L. rhamnosus BMX 54) has been shown in randomized trials and prospective case-control studies to prevent the recurrence of BV and effectively maintain vaginal eubiosis.^89,90

Dietary strategies

Dietary factors affect important processes involved in VLS pathogenesis, including inflammation, oxidative stress, and wound healing. Anti-inflammatory diets such as the Mediterranean diet lead to significant reductions in inflammatory biomarkers and clinical improvements in several inflammatory diseases, including psoriasis and other skin diseases, rheumatoid arthritis, and possibly Hashimoto’s thyroiditis.^91–94 Increasing fresh fruits, vegetables, fish, dietary omega-3 fatty acids, dietary fibers, and probiotic-rich foods, while minimizing animal and processed foods, decreases inflammatory markers and nourishes an anti-inflammatory gut ecosystem.^95,96 Intermittent calorie restriction (CR) may also be beneficial for reducing inflammation in VLS. Like VLS, multiple sclerosis (MS) is characterized by heavy involvement of Th1 in disease onset and progression. A randomized controlled feeding study assessed the effects of eight weeks of intermittent or daily CR diets in people with MS and found that intermittent, but not daily, CR significantly reduced Th1 cells.⁹⁷ Intermittent CR is associated with reductions in inflammatory cytokines in other inflammatory conditions, such as obesity and metabolic syndrome.^98,99 Low oxalate diets have been proposed to potentially decrease the possible role of oxalate deposition in vulvar tissue and are sometimes recommended to patients with VLS, despite limited evidence for their effectiveness. A case report and small studies suggested possible benefits for some women with vulvodynia when low oxalate diets are used in conjunction with calcium citrate supplementation.^100–102 Finally, an elimination diet followed by a food challenge may be useful in identifying specific foods that trigger VLS symptoms, since some women with VLS report specific triggers. A retrospective study in 228 Portuguese VLS patients found that 26% of symptomatic patients reported a worsening of symptoms after consuming a specific food, with pork being the most cited trigger, followed by “spicy food” and “fried food.”¹⁰³

Additional OTC preparations

VLS patients report using a wide variety of over-the-counter topical products, including many natural products containing botanical ingredients for their emollient, barrier, anti-itch, and healing properties. Patients typically learn of these products through online forums and social media. There are several online VLS support groups on Facebook, for instance, where thousands of VSL patients share information about these products, some of which are specifically marketed as VLS treatments. Commonly promoted products and ingredients include coconut oil, emu oil, and branded creams containing botanical medicines such as comfrey, chickweed, and calendula. While virtually no published clinical trials exist for the treatment of VLS with these types of topical preparations, there are anecdotal reports of their benefits in aiding symptom relief and tissue healing. Conversely, some ingredients in these products can lead to vulvar allergic contact dermatitis, which may affect women with preexisting VLS. A cross-sectional analysis of Facebook support groups for VLS found that many of the topical preparations encountered by VLS patients on social media contain vulvar allergens, including fragrances, essential oils, and emollients like propylene glycol, that may lead to vulvar allergic contact dermatitis.¹⁰⁴ Practitioners can guide patients in the appropriate use of allergen-free OTC topical preparations as adjunctive treatments to manage refractory VLS symptoms, so long as they also provide clear explanations about the lack of evidence for their ability to prevent architectural changes or vulvar cancer, which can occur even in the absence of symptoms.

Anecdotal evidence suggests sitz baths with baking soda, Epsom salts, and other ingredients, including borax (sodium tetraborate–not boric acid) may also be helpful to soothe symptoms in some VLS patients. The use of borax in sitz baths is a popular VLS remedy on social media, although there is no published evidence of its safety or effectiveness, and the compound is generally classified as a skin irritant.¹⁰⁵ The British Association of Dermatologists published a statement in 2018 (updated in 2020) recommending against the use of borax by VLS patients due to a lack of safety data.¹⁰⁶

Conclusion

Often unrecognized and misdiagnosed, VLS is a chronic, relapsing inflammatory disorder whose prevalence is likely underestimated. Although its etiology and pathogenesis are still not fully elucidated, it likely involves autoimmunity emerging within a background of environmental and genetic triggers. Untreated or inadequately treated VLS not only impairs quality of life substantially and leads to disfigurement but also significantly increases cancer risk. Ultrapotent topical corticosteroids are the standard of care and decrease cancer risk when used as maintenance therapy; evidence for laser, platelet-rich plasma, and lipofilling therapies is positive and growing. Adjunctive treatment with topical estrogen, oral or vaginal probiotics, dietary modification, and other integrative therapies may also be beneficial. Integrative healthcare practitioners can play an important role in the lives of women with VLS by providing early and accurate diagnosis, evidence-based treatment options, and adjunctive treatments from an overall health perspective.

Biography

Kathleen Jade, ND, is a retired clinician and researcher. She most recently worked as a Research Scientist, Health Data Science Lab, Institute for Systems Biology, Seattle, WA, USA (2019-2022) and as a Clinical Specialist, Arivale, Seattle, WA, USA (2016-2019).