Abstract
This retrospective medical record review evaluates the efficacy of methotrexate for treatment of recalcitrant erosive lichen planus of the vulva in women treated at a vulvar clinic.
Erosive lichen planus of the vulva (ELPV) is a subtype of lichen planus characterized by desquamative, erosive dermatitis involving the vulva and vagina. Management of ELPV is challenging; almost 25% of patients have ELPV that is resistant to first-line therapy with topical corticosteroids.1,2 There are very few studies of ELPV, which makes management of recalcitrant ELPV difficult. Specifically, little evidence is available on methotrexate (MTX) for the treatment of recalcitrant ELPV. The aim of this study was to retrospectively review medical records to evaluate the efficacy of treatment with MTX in women with ELPV at a vulvar clinic.
Methods
The Wake Forest Baptist Hospital Institutional Review Board approved this study. Patient-informed consent was waived owing to the use of deidentified data. A retrospective medical record review was completed to examine women 18 years or older with ELPV treated with MTX from January 2009 through January 2019. Patients were included if they showed clinical features of vulvar lichen planus with the presence of erosions and a consistent biopsy result. Clinical response was defined as a decrease in active inflammation and number of lesions. Disease remission was defined as continued lack of clinical activity in genital mucosa without regular use of prescribed medication. Data analysis was performed from January 2019 through September 2019. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Results
A total of 27 patients with ELPV treated with MTX were identified. Table 1 summarizes the demographic information. Mean time to diagnosis was 3.7 years (range, 1 month to 20 years). Clinical features included well-demarcated erosions, erythematous areas, and Wickham striae. Additionally, 19 patients (70%) had concomitant oral lichen planus.
Table 1. Characteristics of Women With Erosive Lichen Planus of the Vulva Treated at a Vulvar Clinic From January 2009 Through January 2019.
| Characteristic | Value, No. (%) (N = 27) |
|---|---|
| Age at diagnosis | |
| Mean (SD), y | 61.7 (14.0) |
| Median (range), y | 64 (41-80) |
| Time to diagnosis, mean (range) | 3.7 y (1 mo-20 y) |
| Race | |
| White | 25 (93) |
| African American | 2 (7) |
| Site of lichen planus disease | |
| Vulvar mucosa | 27 (100) |
| Vulvar mucosa only | 7 (26) |
| Vaginal mucosa | 6 (22) |
| Oropharyngeal mucosa | 19 (70) |
| Skin | 5 (19) |
| Disease symptoms | |
| Pruritus | 11 (41) |
| Burning sensation | 11 (41) |
| Pain | 8 (29) |
| Erosions | |
| Erythema | 8 (30) |
| Wickham striae | 7 (26) |
| Scarring | 7 (26) |
| Erythema and Wickham striae | 5 (19) |
| Biopsy site | |
| Oral | 8 (30) |
| Vulvar | 6 (22) |
| Cutaneous | 4 (15) |
| Vulvar (previous physician) | 5 (19) |
| Oral (previous physician) | 2 (7) |
| Cutaneous (previous physician) | 1 (4) |
| Unspecified | 1 (4) |
| Histopathologic characteristics | |
| Bandlike infiltrate at dermoepidermal junction | 11 (41) |
| Foci of lichenoid inflammation | 5 (19) |
| Unspecific inflammation | 4 (15) |
| Ulceration and lichenoid mucositis | 3 (11) |
| Lichenoid mucositis | 3 (11) |
| Unspecified | 1 (4) |
| Criteria for diagnosis | |
| Clinical and histologic | 26 (96) |
| Clinical | 1 (4) |
| Other conditions | |
| Vulvodynia | 4 (15) |
| Thyroid disease | 2 (7) |
| Psoriasis | 1 (4) |
| Rosacea conjunctivitis | 1 (4) |
| Fibromyalgia | 1 (4) |
| Herpes simplex virus type 1/2 | 1 (4) |
| Previous medications | |
| Clobetasol | 8 (30) |
| Prednisone | 6 (22) |
| Methotrexate | 5 (19) |
| Hydroxychloroquine | 4 (15) |
| Betamethasone | 3 (11) |
| Clotrimazole | 3 (11) |
| Lidocaine | 2 (7) |
| Mycophenolate mofetil | 2 (7) |
| Fluocinonide | 2 (7) |
| Conjugated estrogens | 2 (7) |
| Acitretin | 1 (4) |
| Triamcinolone | 1 (4) |
| Topical cyclosporine | 1 (4) |
| Hydrocortisone suppository | 1 (4) |
All patients had biopsy results that confirmed lichen planus. The most common biopsy sites were the oral mucosa (8 of 27 [30%]) and the vulva (6 of 27 [22%]). Previous medications included topical corticosteroids and other systemic immunosuppressants (Table 1).
All 27 patients received treatment with MTX, with a mean dose of 12.5 mg for a mean (range) duration of 15.6 (1-56) months (Table 2). A total of 19 patients (70%) reported improvement with MTX use, with 14 patients (52%) reporting improvement at 1-month follow-up. Eleven patients (41%) reported experiencing adverse effects, the most common being fatigue and gastrointestinal distress. At the time of this analysis, 8 patients (30%) continued to take MTX and 19 patients (70%) had stopped. Eight patients (30%) stopped because of adverse effects; of these, 6 patients (22%) maintained clinical improvement and 2 (7%) did not. Five patients (19%) ended treatment with MTX because of remission, 4 patients (15%) improved but were lost to follow-up, and 2 patients (7%) were transitioned to treatment with mycophenolate mofetil.
Table 2. Treatment With Methotrexate (MTX).
| Characteristic | Value, No. (%) (N = 27) |
|---|---|
| Dose, mg | |
| Mean | 12.5 |
| Median (range) | 10 (7.5-20) |
| Duration, mean (range), mo | 15.6 (1-56) |
| Response | |
| Improvement reported | 19 (70) |
| No improvement reported | 4 (15) |
| Lost to follow-up | 4 (15) |
| Current medication | 8 (30) |
| Treatment cessation | |
| Because of adverse effects | 8 (30) |
| Because of remission | 5 (19) |
| Because of inefficacy | 2 (8) |
| Lost to follow-up | 4 (15) |
| Reported adverse effects | 11 (41) |
| Fatigue | 6 (22) |
| GI distress | 4 (15) |
| Hair loss | 2 (7) |
| High blood pressure | 2 (7) |
| Abnormal LFT results | 1 (4) |
| Cramping | 1 (4) |
| Concomitant medications | |
| Topical, compounded | 25 (93) |
| Clobetasol | 21 (78) |
| Triamcinolone | 8 (30) |
| Fluocinonide | 5 (19) |
| Halobetasol | 1 (4) |
| Tacrolimus | 15 (56) |
| Gabapentin | 6 (22) |
| Doxepin | 5 (19) |
| Mycophenolate mofetila | 4 (15) |
| Prednisone | 3 (11) |
| Silver sulfadiazine | 2 (7) |
| Estradiol | 2 (7) |
| Colchicine | 1 (4) |
| Cancer diagnosis | 3 (11) |
| Oral SCC | 2 (7) |
| Thyroid cancer | 1 (4) |
Abbreviations: GI, gastrointestinal tract; LFT, liver function test; SCC, squamous cell carcinoma.
Two patients were already receiving mycophenolate mofetil when they began treatment with MTX and continued concomitantly. An additional 2 patients started treatment with mycophenolate mofetil concomitantly and continued after MTX treatment was suspended.
All patients received concomitant topical treatments, most often clobetasol (21 of 27 patients [78%]) (Table 2). Fifteen patients (56%) received instructions to apply tacrolimus (1 mg capsule dissolved in 0.5 L of water) with gauze for vulvar lesions. Concomitant systemic medications included gabapentin, prednisone (short course), and mycophenolate mofetil. Malignant neoplasms developed in 3 patients (11%): no patients had vulvar squamous cell carcinoma, 2 patients developed oral squamous cell carcinoma, and 1 patient developed thyroid cancer.
Discussion
Disease management in this study highlights the challenge of ELPV. Some studies suggest that topical tacrolimus has efficacy when ELPV is recalcitrant to topical corticosteroids.3 Currently, to our knowledge, there are no good evidence-based recommendations for systemic treatment of ELPV.2,4 A few studies report the efficacy of other systemic therapies, such as oral corticosteroids, antibiotics, antifungals, mycophenolate mofetil, and hydroxychloroquine, in treatment of ELPV.5,6 Although this study cites a good response to MTX, other studies2 have reported poor responses to MTX. Nevertheless, it seems that treatment is often difficult and unsatisfactory. One possible explanation is that systemic therapy is only commenced if there is an inadequate response to topical treatment. Therefore, patients receiving systemic therapy may have more severe disease that is less likely to respond.
Limitations of this study include a small patient population, the concomitant use of topical tacrolimus, loss to follow-up, and evaluation of patients from only 1 vulvar clinic. Although more than 50% of patients with ELPV maintained improvement with MTX, additional studies are needed to support these findings.
References
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