CHAPTER 40 Benign disease of the vulva and the vagina
Development and Anatomy
The vulva consists of the labia majora, labia minora, mons pubis, clitoris, perineum and the vestibule. The labia join anteriorly at the anterior commissure and merge posteriorly into the perineum, the anterior margin of which is the posterior commissure. From puberty, the mons and lateral parts of the labia majora are covered in strong coarse hair and are distended with subcutaneous fat. In addition to hair follicles, they contain sebaceous and sweat (eccrine and apocrine) glands. The labia minora are two smaller, longitudinal, cutaneous, non-hair-bearing folds medial to the labia majora and extending from the clitoris for a variable distance beside the vestibule to end before reaching the perineum. The labia majora and minora are separated from each other by the interlabial fold, and may contain prominent or tortuous veins during pregnancy and later life. The labia minora contain numerous blood vessels, nerve endings and sebaceous glands. There is considerable variation in size and shape from woman to woman, and gross enlargement or asymmetry can occur. Anteriorly, they fuse above the clitoris to form the prepuce and below the clitoris to form the frenulum. The labia minora have an important role during sexual arousal when they become engorged and extend or are pushed outwards to allow coital entry; when flaccid, they serve to protect the vestibule and access to the urethra and vagina (O’Connell et al 2008).
Classification of Vulval Disease
Terminology of lesions and conditions of the vulva has caused confusion because of the many and complex names used, sometimes for similar changes. The International Society for the Study of Vulvovaginal Disease (ISSVD) has published a classification of vulvar dermatoses (Lynch et al 2007) (Box 40.1). Its use is not universal but it serves as a starting point to group some of the diseases described in this chapter.
Presentation of Vulval Disease
The onset of symptoms will sometimes be associated with other life events such as following a course of antibiotics, a diagnosis of certain medical disorders, the introduction of certain therapeutic drugs or withdrawal of systemic corticosteroids. A full medical history will sometimes identify other conditions with vulval manifestations, and dental details should not be overlooked. Some patients with vulvovaginal lichen planus will already have a diagnosis of oral lichen planus; Belfiore et al (2006) found that 57% of women with oral lichen planus also had vulval lichen planus. Many patients will present with a list or bag full of topical treatments that they have used previously. A comprehensive list is useful because those drugs that have helped or caused deterioration can be identified, and this will also allow confident prescription of a preparation not yet tried.
Examination of the Patient
A combined clinic conducted by gynaecologists, dermatologists and genitourinary physicians has considerable merit (McCullough et al 1987). Facilities should include adequate lighting, a tilting examination chair to obtain access to the posterior part of the pudendum, a colposcope, and a camera for colpophotography and clinical photography.
Colposcopic assessment of the vulva is not essential if there is an obvious, readily diagnosed lesion and there are no suggestions of neoplastic change. However, colposcopy is valuable if the patient is symptomatic but no lesion can be seen, if there is difficulty in interpreting or defining the limits of the visible lesions, and to select an appropriate site for biopsy. The techniques are described elsewhere (MacLean and Reid 1995). The vascular patterns can be complex and may be associated with neoplasia. Sometimes, sites of previous biopsies will develop unusual vascular patterns associated with healing. Excessive applications of potent topical corticosteroids will exaggerate vascularity with prominent telangiectasia and thinned epidermis.
Once the vulva has been scanned with the colposcope, aqueous acetic acid solution should be applied. It is important to realize that the aceto-white changes will not be as dramatic as those seen on the cervix, and may not be apparent in areas of abnormal keratinization. Aceto-white epithelium may represent vulvar intraepithelial neoplasia (VIN) or viral changes with human papilloma virus (HPV) and Epstein-Barr virus, as well as tissue repair with ulcers and erosions, scratch damage or coital trauma. It is incorrect to interpret the papillae seen in the vestibule as ‘microwarts’; Jonsson et al (1997) showed that aceto-white changes in the vulva were a poor predictor of viral presence.
In the past, histological diagnosis of the vulval lesions depended on inpatient biopsy performed under general anaesthesia. Very appropriate biopsy material can be obtained using a 4 mm diameter Stiefel disposable sterile biopsy punch, and this can be performed as an outpatient procedure under local anaesthesia (McCullough et al 1987). A silver nitrate stick with a small plug of cotton wool or, alternatively, ferric subsulphate (Monsel’s solution) is applied for haemostasis.
Prevalence of Vulval Lesions
Box 40.2 shows the range of lesions seen in a combined vulva clinic (MacLean et al 1998). There may be some bias in these figures because the clinic received referrals from gynaecologists, and because the authors’ research interests included vulval precancer and pain.
Box 40.2
Prevalence of vulval lesions seen in 1000 women
| Lichen sclerosus | 243 |
| Dermatitis/lichen simplex | 56 |
| Lichen planus | 23 |
| Localized provoked vulvodynia | 98 |
| Generalized vulvodynia | 32 |
| Psoriasis | 25 |
| Diabetic vulvitis | 9 |
| Vulval Crohn’s disease | 5 |
| Acute contact vulvitis | 2 |
| Cicatricial pemphigoid | 2 |
| Plasma cell vulvitis | 2 |
| Neoplastic | |
| Cancer | 23 |
| VIN, usual type | 82 |
| Paget’s disease | 4 |
| Melanoma | 2 |
Source: MacLean AB, Roberts DT, Reid WMN 1998 Review of 1000 women seen at two specially designated vulval clinics. Current Opinion in Obstetrics and Gynaecology 8: 159–162.
Dermatoses
While dermatologists will have little difficulty in reaching a diagnosis with these lesions, most gynaecologists are likely to be less certain. One of the confusing issues is the interchangeable use of the terms ‘eczema’ and ‘dermatitis’; essentially they mean the same thing. Dermatitis is found in 64% of patients with chronic vulval symptoms (Fischer et al 1995). Many of these patients will have skin manifestations elsewhere and will be identified by history and examination. The term ‘atopic dermatitis’ is used when there is clinical evidence of atopy (e.g. asthma, hayfever or allergic rhinitis in the patient or immediate family). In some cases, biopsy and histology will be diagnostic. Many lesions will respond to topical corticosteroids, although the required potency will depend on the diagnosis.
Contact and irritant dermatitis
Clinically, there is a diffuse erythema and oedema with superimposed infection or lichenification. Patch testing may identify the allergen to allow removal or avoidance of the factor, and moisturizing cream or mild steroids should provide local control. Haverhoek et al (2008) reported that 81% of the patients that they saw with vulval pruritus had at least one contact allergen detected on patch testing.
Lichenoid lesions and vulval intraepithelial neoplasia
Terms such as ‘ichthyosis’, ‘leucoplakia’, ‘kraurosis’, ‘lichen planus sclereux’ and ‘dystrophy’ have created confusion in describing vulval lesions (Ridley 1988). The current terminology has evolved from the ISSVD’s 1976 classification of hyperplastic dystrophy, lichen sclerosus (no longer with ‘et atrophicus’) and mixed dystrophy; the abandonment of the term ‘dystrophy’ (MacLean 1991); and the use of the term ‘non-neoplastic epithelial disorder of vulval skin and mucosa’ (Ridley et al 1989) which included lichen sclerosus, squamous cell hyperplasia (formerly hyperplastic dystrophy) and other dermatoses. This did not cover those lesions with neoplastic potential or association, and the latest terminology incorporates ‘differentiated vulvar intraepithelial neoplasia’ for those lichenoid lesions with basal atypia and a significant association with vulval cancer (Sideri et al 2005, Scurry and Wilkinson 2006). This new terminology has met opposition, firstly because it removes the VIN 1, 2 and 3 classification which sat comfortably with CIN 1, 2 and 3 of the cervix, and replaces it with a single-grade system VIN (which groups together VIN 2 and 3 plus differentiated VIN). VIN 1 is uncommon compared with CIN 1. There is no evidence that it is a cancer precursor, and it is best considered as a warty lesion with no need for treatment and follow-up as one would do for the former VIN 2 and 3 lesions. The VIN frequently associated with HPV is now known as ‘usual or classic type’ (sometimes divided into basaloid and Bowenoid or warty subtypes, but this is not always meaningful because both subtypes are linked with HPV 16, and both appearances can occur in the same vulva). On the other hand, atypia or abnormality confined to the basal layer of lichen sclerosus (previously designated ‘hyperplastic/hypertrophic or mixed dystrophy with atypia’ may appear consistent with VIN 1 but has a significant association with vulval carcinoma, and thus differentiated VIN is regarded as high grade (Jeffcoate and Woodcock 1961, Leibowitch et al 1990, Scurry et al 1997). There are opinions that differentiated VIN is only found in the immediate vicinity when vulval cancer develops within an area of lichen sclerosus, but also a growing awareness of the basal cell changes (e.g. overexpression of p53, Ki-67 and CD1a) (Mulveny and Allen 2008) to provide the diagnosis in biopsies taken when cancer is not coexistent. Such cases are believed to have a greater risk of progressing to invasive cancer than cases with lichen sclerosus alone. Eva et al (2008) reported that there is an almost four-fold higher risk of recurrence when vulval cancer occurs in association with differentiated VIN.
Lichen sclerosus
The importance of lichen sclerosus is that it is common, occurring in at least one in 800 girls (Powell 2006) and increasing to one in 30 elderly women (Leibovitz et al 2000). It accounts for up to one-quarter of women seen in vulval clinics (MacLean et al 1998), 1.7% of patients seen in general gynaecological practice (Goldstein et al 2005) and 0.3–1 per 1000 of all new patients seen in a general hospital (Wallace 1971). It occurs in men, where it is known as balanitis xerotica obliterans, but at approximately one-sixth to one-tenth of the incidence in women. It is an inflammatory dermatosis and is frequently symptomatic, causing pruritus, sleeplessness, dyspareunia and constipation. It may produce major architectural changes and alteration in vulval appearance and function, and has a small but important risk of cancer; 60–70% of vulval squamous cell cancers occur against a background of or in association with lichen sclerosus. Lichen sclerosus involves the pudendum, either partially or completely as a figure-of-eight lesion encircling the vestibule and involving the clitoris, labia minora, inner aspects of the labia majora and the skin surrounding the anus. It is usually bilateral and symmetrical. It does not involve the vestibule or extend into the vagina or anal canal.
The lesions consist of thin, pearly, ivory or porcelain white crinkly plaques. Sometimes, there is marked shrinkage and absorption of the labia minora, coaptation of the labia across the clitoris to form a phimosis, and narrowing of the introitus to obscure the urethra and make intercourse impossible. Scratching will produce lichenification or may produce epidermal erosion and ulceration. Areas of ecchymoses and subsequent pigmentation are common. Lichen sclerosus may also involve the trunk or limbs in 18% of patients (Meyrick-Thomas et al 1988).
The histological features of lichen sclerosus typically show epidermal atrophy, dermal oedema, hyalinization of the collagen and subdermal chronic inflammatory cell infiltrate. There is a correlation between clinical appearance and histology, with the clinically thin area showing marked epidermal thinning with loss of rete ridges and vacuolation of the basal cells, while thick white fissured areas will histologically show hyperkeratosis, parakeratosis (abnormal keratinization) acanthosis and elongation, widening and blunting of the rete ridges (lichen sclerosus with lichenification; Ridley 1988). The inflammatory infiltrate may extend into the superficial dermis. These histological features are often modified secondary to trauma, with the presence of red blood cells or haemosiderin. However, histological changes may be minimal, and the histology may appear normal in some clinically obvious cases.
Cause of lichen sclerosus
The aetiology of lichen sclerosus remains unknown. Its uneven distribution between countries raises the possibility of an infectious cause (e.g. Borrelia burgdorferi spread by tick bites), but while there has been demonstration of these spirochaetes (Aberer and Stanek 1987), subsequent studies have not supported this theory.
The possibility of a hormonal (androgen-associated) cause has been examined without conclusive results (Friedrich and Kalra 1984, Kohlberger et al 1998). There is recognition that the incidence is higher among postmenopausal women, but no evidence that it is due to oestrogen deficiency. Young girls with lichen sclerosus seem to gain symptom improvement at puberty, but one study has documented that 75% of these teenagers have persistent features of lichen sclerosus (Powell and Wojnarowska 2002).
The suggestion that lichen sclerosus might be related to an autoimmune process is supported by finding associations with other autoimmune manifestations, a family history of autoimmune-related disease in first-degree relatives or the presence of circulating autoantibodies in patients with lichen sclerosus (Goolamali et al 1974, Meyrick-Thomas et al 1988). Recently, circulating basement membrane zone antibodies have been found in the serum of patients with lichen sclerosus (Howard et al 2004), and a specific circulating autoantibody to extracellular matrix protein 1 (ECM1) has been described (Oyama et al 2003). The nature of ECM1 epitopes in the serum of patients with lichen sclerosus has been examined, and an enzyme-linked immunosorbent assay has been developed which is highly sensitive and specific for lichen sclerosus, and discriminates between lichen sclerosus and other disease/control sera (Oyama et al 2004). Higher anti-ECM1 titres correlated with more longstanding and refractory disease and cases complicated by carcinoma. The factors that initiated this antibody are unknown, or its appearance may predate the development of lesions or symptoms. Investigation of the inflammatory process has demonstrated oxidative damage to lipids, proteins and DNA in biopsies taken from untreated patients with lichen sclerosus (Sander et al 2004
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
