Vaginal involvement in genital erosive lichen planus

Acta Obstetricia et Gynecologica. 2010; 89: 966 970 SHORT REPORT Vaginal involvement in genital erosive lichen planus ANNE LISE ORDING HELGESEN 1,2,3, PETTER GJERSVIK 3,4, PETER JEBSEN 5, ROLF KIRSCHNER 2 & TOM TANBO 1,2,4 1 The National Resource Centre for Women s Health, Oslo University Hospital, Norway, 2 Department of Obstetrics and Gynecology, Oslo University Hospital, Norway, 3 Department of Dermatology, Oslo University Hospital, Norway, 4 University of Oslo, Norway, and 5 Department of Pathology, Oslo University Hospital, Norway Abstract A specialized Vulva Clinic with dedicated gynecologists and dermatologists was established in Oslo, Norway, in 2003. Fifty-eight women referred to the clinic in 2003 2009 were diagnosed with genital erosive lichen planus. All patients filled out a questionnaire. Gynecological examination, including vaginal inspection, was performed, if necessary in general anesthesia. Median age at symptom start was 51 years (range 17 78 years) with 15 women (26%) being younger than 40 years old. Sexual abstinence was reported by 36 women and dyspareunia by another 10. On examination, vaginal involvement was seen in 49 women, including vaginal synechiae in 29 and total obliteration of the vagina in 9. Of 56 women treated with topical corticosteroids for at least three months, two had complete response and 36 partial responses. Similarly, of 22 women treated with tacrolimus, three had complete and six partial response. We conclude that vaginal involvement is more common in genital erosive lichen planus than previously reported. Key words: Lichen planus, vulvar diseases, vaginal diseases, dyspareunia Introduction Lichen planus is an inflammatory disease affecting both skin and mucous membranes (1). The cause is unknown, but recent data suggest the disease to be a T-cell-mediated autoimmune disorder (1,2). Most patients are between 40 and 60 years with a slight predominance of women (3,4). The diagnosis of cutaneous lichen planus is based on the clinical appearance of violaceous polygonal papules and plaques and white lace-like stripes, called Wickham s phenomenon, typically on wrists or feet. Typical findings on histological examination of a skin biopsy will in most cases confirm the diagnosis (4). Mucous membrane involvement of lichen planus occurs in up to two-thirds of the cases, more often in the oral cavity than in the genitalia (4). In genital lichen planus, lesions can be papulosquamous, hypertrophic or erosive, with the erosive type being most frequent, involving mucous membranes only (4). Genital erosive lichen planus is characterized by erythema eventually surrounded by a white lazy border and painful scarring vulvar erosions which may extend into the vagina (5,6) (Figure 1). In contrast to the cutaneous form of lichen planus, histological findings in genital erosive lichen planus are often inconclusive (5 7). Immunofluorescence findings are only indicative for genital lichen planus and may exclude autoimmune bullous skin diseases (1), which are strongly associated with other cutaneous lesions. While the cutaneous form of lichen planus usually subsides within 2 4 years, mucosal lesions tend to be more chronic (8), resulting in long-lasting itching and pain. Scarring is not uncommon and may lead to major anatomical changes, such as absorption of labiae, synechiae of clitoris, stenosis of introitus and total obliteration of the Correspondence: Anne Lise Ording Helgesen, Oslo University Hospital, National Resource Centre for Women s Health, 0027 Oslo, Norway. E-mail: anneliseord@yahoo.no (Received 11 September 2009; accepted 4 February 2010) ISSN 0001-6349 print/issn 1600-0412 online Ó 2010 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) DOI: 10.3109/00016341003681231

Vulvovaginal erosive lichen planus 967 Figure 1. Patient with erosive lichen planus in the vulva. vagina (1,6). As a consequence of these anatomical changes, normal sexual activity is often impossible. There are few treatment options and no curative therapy for women with genital erosive lichen planus, often leading to sexual problems and severe impact on quality of life (9). In 2003 a special Vulva Clinic with a dedicated dermatologist and two gynecologists was established at Oslo University Hospital Rikshospitalet to serve as a nation-wide referral center for women with chronic vulvar pain, infections and skin disease (10). There are few studies on genital erosive lichen planus in women, and most of them are focused on vulvar involvement; in some studies clinical examination of the vagina was not even included (5,6). To our knowledge there are no published studies on the sexual function in these patients. We report symptoms and clinical and histological findings in all women with genital erosive lichen planus referred to the Vulva Clinic in Oslo during the period 2003 2009 with special emphasis on vaginal involvement and its influence on sexual function. Material and methods All women diagnosed with genital erosive lichen planus at the Vulva Clinic between 1 January 2003 and 30 April 2009 were included in this retrospective case series. The women filled out a questionnaire before first consultation, including questions on parity, previous gynecological history, skin disease, age at symptom onset, sexual activity, and dyspareunia. A regular case history, including information on previous treatment, was obtained by the dermatologist and/or gynecologist at the Vulva Clinic. In all women, at least one complete gynecological and oral examination was performed. If vaginal stenosis or local pain made vaginal inspection impossible, further examinations were performed in general anesthesia. If a representative biopsy had not been taken previously or was inconclusive, a biopsy from an affected mucosal area was performed. All biopsies (except six) were re-examined by one experienced pathologist, using established criteria for genital erosive lichen planus, i.e. wedged-shaped hypergranulosis, degeneration of the basal layer, colloid bodies, and a band-like lymphocytic infiltrate at the dermo-epidermal junction (11). Patients with biopsies showing predominance of plasma cells (> 50% of the infiltrate) were diagnosed with plasma cell vulvitis and excluded from the study, except four women with typical clinical signs of erosive lichen planus. The histological findings were then graded as diagnostic for genital erosive lichen planus, consistent with, but not diagnostic for this diagnosis, or non-specific. Immunofluorescence examination was done in 22 biopsies. The diagnostic criteria of genital erosive lichen planus were based on the clinical appearance of typical mucosal lesions, as described above, in some cases supported by histological diagnosis. In most cases the clinical diagnosis was made by at least two of the clinic s attending clinicians, examining the patient together. Patients in whom we had clinical or histological doubt as to whether they had lichen planus or lichen sclerosus of the vulva, were excluded. The border between vulva and vagina was defined as the hymenal ring area. Symptoms, clinical findings, treatment, and treatment response were recorded at every visit. Treatment response was categorized as complete response (complete resolution), partial response (less erythema and/or fewer erosions) or no response (persistent findings or worsening), as evaluated by the doctor and by the patient separately. Clinical data from the medical records were made anonymous and assessed according to approval from the Data Protection Officer, Oslo University Hospital Rikshospitalet. The study was performed in accordance with the Helsinki Declaration of 1964. Results Of 989 women referred to and examined at the Vulva Clinic during the period 2003 2009, 58 women (5.9%) were diagnosed with genital erosive lichen planus. Median age at time of onset of symptoms was 51 years (range 17 78 years) with 15 women (25.9%) being younger than 40 years. Median time from symptom start until diagnosis (made either before or at the Vulva Clinic) was three years (range 0 37 years), and median age at diagnosis 56 years (range 23 81 years). All but two women had been pregnant once or more.

968 A.L.O. Helgesen et al. In 27 women, the diagnosis had been made previously, either by a gynecologist (n = 17) or a dermatologist (n = 13) and confirmed at the Vulva Clinic. In 28 women, the diagnosis was made at the Vulva Clinic. Median number of consultations at the Vulva Clinic was three (range 1 21). Table 1 shows symptoms, clinical features, and sexual function reported by the women at the first consultation. Information about sexual function was reported by 51 patients, including 36 women (70.6%) reporting sexual abstinence (median abstinence time three years; range 0.6 15 years). Extragenital lichen planus was reported by 35 women, including 33 women with oral lichen planus, of whom 20 had genital symptoms before the onset of oral symptoms. Some patients reported hypothyroidism (n = 12), hypertension (n = 11), allergy (n = 13), obesity (n = 8), diabetes (n = 5), asthma (n = 3), or carcinoma in situ of the cervix, grade III (CIN III) (n = 1). Types and location of lesions are also included in Table 1. In 4 women (6.9%) only vulva was involved, while both vulva and vagina were involved in 31 women (53.4%). In 18 women (32.7%), only vagina was affected; of these 15 women had both proximal and distal vaginal lesions. Of the 49 women with vaginal involvement, 29 had developed varying degrees of stenosis, including total vaginal obliteration in 9 women. Biopsies from vulva or vagina were available for histological examination in 49 women. Two biopsies showed vaginal adenosis in addition to genital erosive lichen planus. Histological examination was performed in 15 of 18 women with vaginal involvement only. In 10 of these patients, the histological findings were either diagnostic or consistent with lichen planus. No case of neoplasia was diagnosed. Biopsies from the vulva or vagina were available for immunofluorescence examination in 22 women (Table 1). In women with vaginal involvement only, immunofluorescence examination was performed in 10 (of 18), showing findings consistent with erosive lichen planus in five patients and non-specific in another five. Twenty-seven women had tried topical application of corticosteroids with different potency before attending the Vulva Clinic, some for up to 10 years. At the clinic, treatment was initiated in all women, most often with topical corticosteroids (n = 56), i.e. ultrapotent cream or ointment on vulvar lesions and low potent foam on vaginal lesions. In addition, some women were treated with topical tacrolimus (n = 22), systemic treatment with prednisolon (n = 5), retinoids (n = 2), azathioprine Table 1. Clinical and biopsy features in 58 women with vulvovaginal erosive lichen planus examined and diagnosed at a specialized Vulva Clinic in Oslo, Norway, 2003 2009. Number of patients Symptoms Genital itch 28 Genital pain 52 Sexual abstinence 36 (of 51) No dyspareuni 5 (of 15) Dyspareuni 10 (of 15) Extragenital lichen planus Oral mucosa 33 Esophagus 1 Extragenital skin 6 Localization of lesions Mucosal vulva 39 Lower vagina 43 Upper vagina 39 Perianal skin 10 Clinical findings Mucosal erythema 58 Mucosal erosions 47 Vulval synechiae 21 Vaginal synechiae 29 Vaginal obliteration 9 Histology Diagnostic for lichen planus 14 Consistent with lichen planus 21 Non-specific 14 a (4) Not performed 9 Immunofluorescence Consistent with lichen planus 7 Non-specific 15 Not performed 36 a Included four patients with plasma cell vulvitis. (n = 2), ciclosporin (n = 6), tumor necrosis factor (TNF)-a-blockers (n = 1), methotrexate (n = 2), or surgical treatments (n = 17) (Table 2). In women treated with topical steroids (n = 56), two patients had complete response, 36 partial response, and 18 no response, as evaluated by the doctor after three months treatment or more. Similarly, three of 22 women treated with topical tacrolimus ointments had complete response, six partial response and 13 no response. There was good agreement between the symptomatic response reported by the women and the evaluation by the doctor based on visual inspection at followup visits. In 17 women digital or instrumental dilatation, alternatively CO 2 -laser vaporization, was performed in order to open synechiae in the vulva and/or vagina. Patients were then instructed to apply topical steroids and perform vaginal self-dilatation several times a week postoperatively. Most of these patients (n = 13) reported good relief, although to a varying degree and often with some recurrence.

Vulvovaginal erosive lichen planus 969 Table 2. Overview of treatments tried in 58 women with vulvovaginal erosive lichen planus attending the Vulva Clinic in Oslo, Norway, 2003 2008. 1st 2nd 3rd 4th 5th Topical treatment Corticosteroids 52 3 1 Tacrolimus 2 14 4 1 1 Systemic treatment Prednisolon 1 3 1 Azathioprine 1 1 Retinoids 1 1 Methotrexate 1 1 Cyclosporine 1 2 1 1 1 Infliximab 1 Surgery/dilatation 1 11 4 1 Note: Many patients tried several treatments, i.e. up to five. Discussion The prevalence of erosive lichen planus in the general population is unknown. The number of women in this case series constituted 5.9% of all referrals to the clinic. In two other studies, 3 and 8% of new patients referred to a specialized vulva clinic due to vulvar pain were found to have erosive lichen planus (12,13). In our patients, approximately 26% were below 40 years at the time of diagnosis, indicating that genital erosive lichen planus is not mainly a peri- or postmenopausal disease, as has been stated by some authors (5,6). The median age at diagnosis was 51 years, which is lower than reported by Kirtschig et al. (5) and Cooper (6), but similar to Kennedy and Galask (12). Median interval time between onset of symptoms and time of diagnosis was shorter than in other studies (6,12). This may reflect a lower threshold for referring patients from primary and secondary to tertiary care in Norway, especially after the establishment of the Vulva Clinic. All but nine of our patients with genital erosive lichen planus had vaginal involvement, including 18 patients with vaginal lesions only. Clinical and biopsy features, including histology and immunofluorescence, did not indicate any other disease. The high rate of isolated lesions in the vagina has not been described in previous studies. The total rate of vaginal involvement is somewhat higher than in two smaller patient series, in which vaginal involvement were found in 14 of 20 patients (14) and 11 of 19 patients (7), respectively. In larger studies, the vagina was not examined routinely and vaginal involvement was therefore unknown in most patients (5,6). The author of one of these reports stated that it proved impossible to examine the vagina adequately in all patients because of pain or narrowing of the introitus (6). Also, the hymenal ring, the natural border between vulva and vagina, is often more difficult to identify in elderly women, especially with local scarring. Possibly, the border between vulva and vagina may be defined differently in various studies. Involvement of the upper part of vagina was found in more than two thirds of our patients. This emphasizes the importance of total vaginal examination in patients with genital erosive lichen planus. In our study, all patients were examined vaginally, when necessary under general anesthesia. Two-thirds of our patients reported several years with sexual abstinence, and about 2/3 of those with sexual activity had dyspareunia. This emphasizes the importance of addressing sexual functions when examining patients with genital lichen planus. Other reasons for sexual abstinence, however, cannot be excluded (15). Other limitations of our study include the use of referral documents for recording treatment in a majority of the patients. Contrary to other studies, no case of vulvovaginal neoplasia was diagnosed. However, the number of patients was relatively low and the observation period short. In a larger case series in the UK 7 of 114 women developed vulvar intraepithelial neoplasia and 3 women squamous cell carcinoma during a five-year observation period (6). In another case series 1 of 44 women developed vulvar carcinoma (5). A variety of treatments were tried, most often topical application of corticosteroids. Of the patients treated with topical corticosteroids, nearly two-thirds had some effect, but only two had a complete remission. This is in accordance with other reports (5,6). Randomized clinical trials have not been performed to document the effect of such treatment. The choice of treatment in genital erosive lichen planus must therefore be based on empirical evidence and clinical experience. Our report supports topical steroid treatment as the first treatment of choice in genital erosive lichen planus. We recommend our standardized practice in the vulvar clinic of close cooperation between dermatologists and gynecologists.

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