Vulval disease

A Drummond, F A Campbell, D T Roberts

HK Pract 2003;25:563-572

Summary

Vulval involvement may be a feature of many types of skin disease and despite their diversity of aetiology and severity, the psychological morbidity may be profound. A sympathetic and reassuring approach to management will help to alleviate embarrassment and fear. After formal diagnosis many patients may benefit from contact with self-help groups or counsellors. This multidisciplinary approach facilitates treatment of pathology and simultaneous resolution of resultant sexual and relationship problems.

摘要

外陰毛病可能是多種皮膚病的象徵。雖然它有不同的成因和嚴重程度，但是對病人的心理可能造成極大憂鬱。 帶同情和安慰的治理方法會減輕病人的不安和害怕。在正式診斷後，很多病人會因聯繫自助小組或輔導員而得益。 這樣的多方位治療方式會利於病理的醫治，同時亦可解決相關的性和人際關係的問題。

Introduction

Vulval disease presents itself to a variety of specialists including primary care physicians, dermatologists, gynaecologists and sexually transmitted diseases (STD) physicians. Virtually all vulval diseases present with either itch, burning, pain or dyspareunia. These diseases may be neoplastic, inflammatory or infective and are the province of the gynaecologist, dermatologist or STD consultant respectively. It is important that the patient be directed to the correct specialist for appropriate management as the symptoms are often non-specific. For this reason multi-disciplinary vulval clinics are now common place in the UK. Such clinics allow an accurate diagnosis to be made and for the patient to be managed thereafter by the appropriate specialist.

The prevalence of vulval disease is unknown and estimates are likely to be low as many women never seek medical advice due to anxiety and embarrassment about their conditions. Most women try "over the counter" preparations prior to presentation. These usually result in little benefit and may aggravate any pre-existing condition. Most women will initially present to their primary care physician and a sympathetic attitude is required to try and alleviate the patients' fears and anxieties. Vulval disease may be chronic, and effective therapy can be elusive, so that many women will require long term medical and psychological support.

The normal vulva and its variants

The vulva refers to the area of skin encompassing the hair-bearing portion of the labia majora to the hymen. There is wide variation in the normal anatomy and degree of pigmentation and erythema of the vulva. The number and size of sebaceous glands over the labia minora varies greatly and can be striking. The large sebaceous glands are called Fordyce spots and are a variant of normal rather than a disease.

Figure 1: Solitary angiokeratoma Figure 2: Vestibular papillomatosis Figure 3: Epidermoid cysts Figure 4: Psoriasis affecting the vulva with well demarcated erythematous plaques Figure 5: Silvery white patches of lichen sclerosis affecting the labia majora Figure 6: Classic lichen planus of the vulva showing Wickham's striae Figure 7: Extensive herpetic eruption in a child Figure 8: Hyperkeratotic plaques of pemphigus vegetans Figure 9: Erythematous white plaques of VIN Figure 10: Large ulcerated nodule confirmed as a squamous cell carcinoma on histology

Angiokeratomas (Figure 1) are seen in 1% of women and present as bright red to almost black lesions. These are benign and require no treatment, although laser therapy has been used to treat them and with success.

In vestibular papillomatosis (Figure 2),  now regarded as a variant of normal,  multiple, asymptomatic, small, round papules spread over the vestibule and the labia minora. These require no treatment but can be mistaken for viral warts.

Epidermoid cysts occur in hair-bearing skin and are common on the labia majora (Figure 3). Again, no treatment is required unless they cause symptoms.

The inflammatory dermatoses

Vulval dermatitis

The prevalence of vulval dermatitis is unknown. Cases are frequently referred to specialist clinics for further investigation and management.¹ The laxity of vulval tissue may cause modification of the normal features of common dermatoses and diagnostic confusion can arise. Examination for classical signs of disease at other sites may provide helpful clues in this respect.

Atopic dermatitis

Atopic dermatitis of the vulva is usually part of a more generalised eruption but symptoms may be exacerbated by local friction, temperature and sweating. Intense itch and subsequent scratching lead to lichenification and secondary infection. Topical steroids will interrupt the itch-scratch cycle but treatment should be supplemented by regular application of emollients and with oral antihistamines if necessary.

Irritant contact dermatitis

Delicate vulval skin is more susceptible to chemical and mechanical trauma than many other body-sites and the history should include detailed questioning about the use of potential irritants such as soaps, bubble-baths, washing powders and fabric conditioners. Sweating may exacerbate irritation as will mechanical trauma from towels or from scratching. Management involves avoidance of fragranced toiletries and detergents, and includes the wearing of loose-fitting clothes made from natural fibres and regular application of emollients. Petroleum jelly acts as a useful barrier ointment. Topical steroids and oral antihistamines are effective in controlling symptoms where simple measures fail.

Allergic contact dermatitis

Allergic contact dermatitis may bear some similarities to irritant dermatitis but oedema and erythema are often prominent features. It can complicate other dermatoses as a result of the application of numerous topical agents which then act as sensitisers. Common culprits are neomycin, local anaesthetic-containing creams, antifungal treatments and spermicides. Fragrances, preservatives and rubber contraceptive devices are also frequently implicated. Management includes allergen avoidance, topical steroids and emollients.

Seborrhoeic dermatitis

Typically seborrhoeic dermatitis affects the groin folds causing waxy, yellow-orange scaling on an erythematous base. Edges may be poorly defined and the eruption often encroaches on the labia majora. The clinical presentation may be further confused by scratching, lichenification and irritant or allergic contact dermatitis. Symptoms usually respond to a topical combination therapy containing steroid and antifungal agents. Signs of seborrhoeic dermatitis at other common sites such as the scalp will help to confirm the diagnosis.

Psoriasis

Psoriasis is a common inflammatory dermatosis that is frequently diagnosed and managed by primary care physicians. Psoriasis of the genital region is common and may occur in isolation, with more widespread flexural involvement (flexural psoriasis) or with psoriasis vulgaris. Typical lesions on the skin are well-demarcated, red thickened plaques covered with silvery scale. Lesions of the hair-bearing genital skin look similar, however lesions elsewhere are less thickened and scaly but still well demarcated (Figure 4). Involvement of the labia minora is uncommon and usually associated with more widespread disease. The phenomenon may play a role in genital psoriasis with heat, sweat and friction producing a mild chronic irritation of the skin. The diagnosis is usually clinical although, occasionally other conditions need to be excluded such as seborrhoeic dermatitis, candida and dermatophyte infection, lichenified eczema, contact dermatitis, extra-mammary Paget's Disease and vulval intraepithelial neoplasia (VIN). Genital psoriasis often follows a chronic course but does not lead to scarring. Treatment is with topical steroids alone or in combination with a topical antifungal or antibiotic agent if secondary fungal or bacterial overgrowth is suspected.

Lichen sclerosus

Lichen sclerosus (formerly lichen sclerosus et atrophicus) is a chronic inflammatory skin disease which predominantly affects women but which also occurs much less commonly in children and in men. Although it may develop at any age it most frequently presents in the 5th or 6th decade with severe pruritus and discomfort especially in a "figure-of-eight" distribution around the vulva and peri-anal area. Although some patients are asymptomatic and detected only on routine examination, others have intractable itch, dysuria and dyspareunia. Clinical changes include patchy or plaque-like pallor (Figure 5), telangiectases, purpura and atrophy. Skin becomes fragile and tender and traumatic fissures may develop with sexual intercourse or after defaecation. Scarring leads to disruption of normal vulval architecture with fusion and ultimately complete resorption of the labia minora as well as tight introital stenosis. In prepubertal patients clinical signs may be mistakenly attributed to sexual abuse and such cases should be handled with care and discretion.

Lichen sclerosus may involve extra-genital sites, most commonly the thighs, submammary areas, neck, shoulders and wrists.² The aetiology is uncertain but several groups, who have found an increased incidence of alopecia areata, vitiligo, thyroid disease and diabetes in these patients, have proposed an autoimmune basis.

Management should be directed at helping the patient to cope with their disease rather than to expect a cure although many younger patients will improve spontaneously at puberty. Avoidance of tight clothing, local friction and irritants in combination with super-potent topical steroids are necessary for symptomatic relief and clinical improvement. These should be used twice daily and tailed off over a three-month period, the total amount of applied steroid not exceeding 30 grams. A small percentage of patients will develop squamous cell carcinoma of the vulva necessitating long term follow up.

Lichen planus

Lichen planus is an inflammatory dermatosis of unknown cause. Involvement of the vulva can occur as part of more widespread disease (skin, scalp, nails and oral mucous membranes) or in isolation. 50% of women with cutaneous disease will have vulval involvement if examined.³ Vulval lichen planus typically presents with soreness but some women describe pruritus, burning, dyspareunia or ulceration. A minority of patients are asymptomatic or have minimal symptoms. Three clinical variants are recognised: classic, hypertrophic and erosive forms. In the classic form, small violaceous papules are present and a reticulate white lacy pattern of Wickham's striae, similar to that seen on the buccal mucosa, may be seen (Figure 6). Hypertrophic lesions can occur on the vulva, the perineal and perianal area. Erosive disease can affect the labia majora, labia minora, vestibule and vagina.⁴ The erosive form has a tendency to be persistent and progressive with the end result being loss of vulval architecture and possibly vaginal adhesions and stenosis. A biopsy is usually required to distinguish vulval lichen planus from other erosive diseases such as bullous disorders, lichen sclerosus, VIN, lupus erythematosus, disease, Crohn's disease and infections. Management can be difficult and is best coordinated in a specialised vulval clinic or by a dermatologist with an interest in vulval disease.

There is some debate about a possible overlap between lichen planus and lichen sclerosis as some patients appear to have both conditions coexisting.⁵ The development of malignancy in vulval disease is reported but the incidence is unknown.⁶ Long-term follow up of these patients is required and early biopsy of any suspicious lesion is important.

Plasma cell vulvitis (Zoon's vulvitis)

This rare condition is benign and can affect all areas of the vulva. Clinically the lesions are red and often haemorrhagic and may mimic lichen sclerosis or lichen planus. A vulval biopsy showing a dermal infiltrate of plasma cells with no cytologic atypia is required to confirm the diagnosis. Treatment is required for relief of pruritus or pain and a trial of corticosteroids is worthwhile. Other treatments advocated include topical flamazine, intralesional corticosteroids, intralesional and oral etretinate.⁷

Infections of the vulva

Perineal skin is warmer and moister than skin elsewhere and supports the growth of commensal organisms as well as transient pathogens. Local flora may be modified by hormonal factors, by disease processes such as diabetes and by environmental factors such as health spa whirlpool baths.

Candidal infection

Candida albicans is frequently a commensal that causes symptoms only when the local environment supports pathogenicity. This may occur in pregnancy or with the use of the oral contraceptive pill or it may develop as a result of local tissue damage due to incontinence or intertrigo. Pruritus may be mild and erythema confined to the introital area but in more severe cases the eruption is red, well demarcated with a vesiculo-pustular edge extending beyond the groin area. There may be satellite pustules distal to this and curd-like vaginal discharge may also be noted. Diabetes should be excluded before treating with a topical imidazole either alone or in combination with a mild to moderately potent topical steroid. Vaginal treatment should be considered either with a clotrimazole pessary or oral fluconazole if discharge is a feature.

Bacterial infections

The hair-bearing area of the vulva may be affected by impetigo, folliculitis or "boils". These are usually due to Staphylococcus aureus infection either as a primary phenomenon or secondary to chronic itch caused by atopic dermatitis, scabies or pubic lice. Oral antibiotics along with treatment of the primary problem will normally lead to resolution.

Viral infections

The three main groups implicated in viral disease of the vulva are the herpes and pox viruses, and human papilloma viruses (HPV). Many strains of HPV exist and there are recognised associations with cervical neoplasia. Sexual promiscuity has led to an increased incidence of infection and lesions may be solitary or confluent with a velvety texture extending to the labia minora. Differential diagnoses include syphilitic condylomata and vulval carcinoma but biopsy should facilitate differentiation. Focal lesions should respond to podophyllotoxin or imiquimod while more extensive involvement may require cryotherapy, diathermy or laser treatment.

Genital herpes is usually caused by HSV2 infection acquired in early adult life (Figure 7). Non-genital HSV1 infections are also common but antibodies to one type do not protect against the other type. Primary genital herpes is frequently more severe and widespread than recurrences and may involve the vagina, urethra and anal canal. Subsequent eruptions may be precipitated by infection, stress or menstruation and patients quickly learn to recognise their prodromal symptoms. Oral antiviral drugs such as aciclovir, famciclovir and valaciclovir are effective but hospital admission and parenteral treatment may be required for severe cases. Herpes zoster may mimic HSV but is classically segmental and extremely painful and may involve motor nerves altering bowel and bladder functions.

Mollusca are caused by a common pox virus and spread either by sexual contact or by autoinoculation from another site. In adults, pubic lesions are more common than vulval lesions and inflamed solitary lesions may be mistaken for simple "boils". Simple local destructive measures such as gentle cryotherapy or expression will speed resolution.

Bartholinitis

Bartholin's glands are bilateral mucus secreting structures whose ducts open into the posterior aspect of the labia minora. Infection as a result of bacterial or venereal disease may cause formation of abscesses, which require surgical intervention to achieve resolution.

Venereal disease

Isolated vulvitis is rare in the context of venereal disease but local inflammation may be a feature of syphilis or gonorrhoea.

Definitions

Fixed drug eruption

In this disorder one to several round, erythematous plaques, blisters or erosions appear at the same site or sites when a particular drug is taken systemically. Genital lesions are common and may affect the vagina as well as the vulva. Paracetamol, penicillins, oral contraceptives, teracyclines, sulphonamides and non-steroidal anti-inflammatory drugs are a few of the common medicines implicated in this condition.

Erythema multiforme and Stevens-Johnson syndrome

These are reactive dermatoses usually triggered by infection or medication. They occur all over the body in all ages, races and affecting both women and men. There is a spectrum of disease severity with Steven-Johnson syndrome having mucous membrane involvement as an essential feature. In the vulva, painful erosions can affect the labia majora, labia minora and vestibule and the vagina may also be involved. The classic cutaneous sign of these eruptions is the target lesion (Figure 4); but in severe disease, lesions may become confluent and blistered and target lesions may be difficult to find. Treatment requires identification and removal of the causative agent with patients sometimes requiring hospitalisation for supportive care and treatment.

Immunobullous diseases

This is a rare group of disorders that present with blistering of the skin and mucous membranes. Anogenital disease is found in approximately half of females with bullous pemphigoid, cicatricial pemphigoid and linear IgA disease.⁸ However, isolated vulval disease is extremely rare and most patients present with more widespread involvement. These patients require to be referred to a dermatologist for diagnosis and management of their conditions.

Bullous pemphigoid mainly affects the elderly and presents with tense blisters arising on an erythematous base. The inner thighs, inguinal creases, perineum and labia majora are the most commonly affected areas of the genitalia. The labia minora are rarely involved but erosions are seen more commonly than intact blisters. This is a non-scarring disorder, unlike cicatricial pemphigoid which produces significant scarring of both the mucous membranes and the skin. In this disease the mouth, eyes and genitalia are frequently involved. The severity of vulval disease is variable but scarring is a prominent feature and vaginal involvement common.

Linear IgA disease of children and adults usually presents with tense blisters over the genitalia, thighs and lower abdomen. The condition may become more generalised and lead to scarring. Childhood disease often remits at puberty.

Pemphigus vulgaris is a very rare blistering disorder of both skin and mucous membranes that presents in middle age. It affects all races but the incidence is higher in Ashkenazi Jews. The blisters are fragile and rupture easily producing painful erosions of the labia majora, labia minora and vestibule. A more benign and chronic variant is called pemphigus vegetans. This is initially indistinguishable from pemphigus vulgaris but in advanced disease hyperkeratotic plaques obscure the blistering nature of the condition (Figure 8).

Hailey-Hailey disease

This is a rare, familial, superficial blistering disease that usually presents in the 3rd or 4th decade. The blistering nature of this condition is difficult to appreciate clinically as the fragile blisters quickly rupture to produce linear erosions, crusting and moist, red malodorous plaques. These plaques expand peripherally with central healing. It affects the genital area, axillae and lateral neck. The disease usually affects the labia majora with spread onto the upper inner thighs. The disease is exacerbated by heat, friction and bacterial or viral infections. Treatment aims to reduce friction and secondary infection. Topical steroids combined with antibacterial and antifungal agents are used in combination with bland emollients. Long-term oral antibiotics and occasionally oral steroids or ciclosporin can be useful.

disease

This is a rare disorder with a spectrum of signs including oral ulcers, genital ulcers, ocular inflammation and skin lesions. Genital ulcers are present in about 90% of patients but vary in location, number and duration. The major differential diagnoses include chancroid, Crohn's disease and genital herpes. The diagnosis and treatment of patients with this disease can be difficult and they are often managed jointly by dermatologist and rheumatologists.

Pigmentary disorders of the vulva

There is considerable variation in vulva pigmentation due to ethnicity, age and hormonal status. Patchy areas of hyper- and hypopigmentation may present to the primary care physician after the woman herself has become aware of these or they have been discovered during examination of the vulva for other medical reasons. The cause of hyperpigmentation may be due to haemosiderin deposition, post-inflammatory pigmentation, hypermelanosis, lentigines, naevi and rarely malignant melanoma. Pigmentary lesions often cause diagnostic difficulty and should always be referred for a specialist opinion and consideration of biopsy.

Hypopigmentation is a common sequela of inflammation and is more common in dark skin. The pigment loss is incomplete and the patches have an ill-defined edge. Vitiligo produces well-defined, symmetrical patches of complete depigmentation that may also be associated with loss of hair pigment.

Tumour of the vulva

Most cysts, swelling, nodules and masses that arise in the vulva are benign and are rarely referred to a dermatologist for diagnosis and management.

Paget's disease

Vulval Paget's disease is the most common type of extra-mammary Paget's disease. It is now recognised as a form of intraepithelial adenocarcinoma.⁹ About 5% of patients have regional neoplasia, such as cervical adenocarcinoma or a genitourinary tract malignancy. A proportion, 6-20%, will have an underlying adenocarcinoma in the skin adnexae or the Bartholin's gland. Most cases are not associated with a locally invasive or distant neoplasm and appear to develop in situ.⁹ Patients tend to be elderly at presentation and may have had vulval itch for a variable interval from a few months to many years. Clinically there are multiple, erythematous, eczematoid, scaly patches or plaques on the labia majora and possibly the perineum and perianal area. A skin biopsy is required to make the diagnosis with the treatment being surgical excision.

Vulval intraepithelial neoplasia

In this article, the term VIN applies to intraepithelial squamous carcinoma and replaces conditions previously known as Bowen's disease, Bowenoid papulosis, erythroplasia of Queyrat and squamous carcinoma-in-situ. The lesions are graded VIN₁, VIN₂ or VIN₃ according to the degree of cytological atypia on histology. The worldwide incidence appears to be increasing, particularly in younger women whose disease tends to be associated with human papilloma virus (HPV). Clinically their disease is multifocal and often associated with lesions in the cervix, vagina and perineal skin. In older women it is not usually associated with HPV, unifocal and restricted to the vulva. Women complain of itch and about one-third will have noticed a change in their vulval skin. A proportion, 18 - 46%, will be asymptomatic and have their disease detected when examined for another reason.¹⁰ The clinical findings are very variable and lesions may be red, white, grey, brown or pigmented (Figure 9). The patches and plaques may be solitary or multiple and flat, granular or warty. A biopsy and full examination of the vulva, vagina and cervix is required in all patients. There is a risk of progression to invasive squamous cell carcinoma and so treatment is required to eradicate the VIN. The mode of treatment may vary depending on the patient, their disease and local expertise.

Squamous cell carcinoma

Squamous cell carcinoma accounts for the vast majority of malignant vulval tumours. In older women it usually arises in a background of lichen sclerosis, whereas in younger women it is related to HPV and VIN. Patients generally present themselves to their primary care physician with a firm, ulcerated nodule (Figure 10) and will be referred to a gynaecologist for diagnosis and management. Occasionally dermatologist and primary care physicians identify these when patients attend for management and follow up of their lichen sclerosis.

Vulvodynia

Vulvodynia is the generic term used to describe vulval discomfort in the absence of any objective physical signs. Classically patients describe burning, stinging or a "raw" sensation and clinical examination yields no diagnostic clues. It is now thought to be of two types, namely: vulvar vestibulitis where symptoms are produced by any contact with the vestibule, and dysaesthetic vulvodynia where cutaneous perception of pain seems to be altered. In the vestibulitis group, burning and dyspareunia are common and tampon insertion, tight clothing, local friction and sexual intercourse aggravate symptoms. The dysaesthetic group tend to be the older females and peri-menopausal with more or less constant symptoms. Dyspareunia is not a feature and discomfort is usually localised to the distribution of the pudendal nerve. Treatment is different for the two groups. Vestibulitis responds to bland emollients and topical steroids whereas the dysaesthetic group should be managed as for neuropathic pain. Oral amitriptyline is a good first-line agent but non-responders may require gabapentin. Both groups require patience, understanding and a sympathetic explanation regarding the benign nature of their condition and the potential for improvement.

Miscellaneous conditions

Lichen simplex chronicus may develop as a secondary phenomenon to pruritus vulvae caused by diabetes or iron deficiency. Appropriate investigation will detect such problems and the pruritus will settle on treatment of the underlying disorder. Many patients with Crohn's Disease have anogenital involvement and this may precede the classical symptoms by many years.¹¹ Oedema may be followed by sinus, abscess and granuloma formation and biopsy should clarify the diagnosis. Lesions usually respond to the chosen systemic therapy for the underlying disease.

In the past, various types of sexual behaviour have been labelled as sexual deviations. In fact historically, the term "sexual deviation" was preceded by that of "sexual perversion", both of which denote a sense of right and wrong, good and bad. According to Bancroft,² sexual deviation denotes "any sexual behaviour which is socially unacceptable, stigmatised, and in many instances legally prohibited". To be more specific, Scott³ defined it as "a sexual act or fantasy other than genital intercourse with a consenting partner of the opposite sex of similar sexual maturity and acceptable blood relationships, and such behaviour is frequently repeated, contrary to cultural norms". With the changing morality in Western countries, the term "sexual deviation" is sometimes changed to "sexual variations" instead. According to de Silva,⁴ it refers to "sexual desires and behaviours outside what is considered to be the normal range". In the U.S., the neutral term "paraphilias" (meaning deviated attractions) is used, and is defined as recurrent, intense sexually arousing fantasies, sexual urges, or behaviours generally involving 1) non-human objects, 2) the suffering or humiliation of oneself or one's partner, or 3) children or other non-consenting persons, that occur over a period of at least 6 months. To qualify fully for such a diagnosis, there should be clinically significant distress or impairment in social, occupational or other important areas of functioning.

Key messages

1. Vulval disease may be inflammatory, infective or neoplastic and may present late as a result of fear or embarrassment.
2. It is best managed by a multi-disciplinary team whose individual expertise contributes to the holistic approach.
3. Vulval disorders may be a local manifestation of a systemic disease and more comprehensive investigation is sometimes required.
4. Patients should be treated with sympathy and understanding since vulval disorders can create major emotional and psychological problems.