Chapter 78. Diseases and Disorders of the Female Genitalia

The incidence and prevalence of dermatoses affecting the female genitalia are generally not well established. The vulva has been referred to as “the forgotten pelvic organ.” Despite being the visible female genital structure, it is least described in the medical literature.1 Teaching about vulvar conditions and even the normal vulva is sadly lacking for most medical practitioners, so it is not surprising that vulvar conditions are both underreported and underdiagnosed. Approximately 16% of women report undiagnosed chronic vulvovaginal pain at some time in their lives.2,3

The etiology and pathogenesis of many diseases of the female genitalia are likewise not well understood. Those that also affect other areas of the body are better characterized, but the environment of the vulva strongly affects the course of disease.

History

The approach to the patient with vulvar complaints requires directed history taking, as outlined in Box 78-1.

Cutaneous Lesions and Symptoms

The warm moist environment of the vulva often alters disease morphology or symptomatology. For example, usually scaling dermatoses may lack clinically obvious scale, and in diseases that usually exhibit well-demarcated plaques, the lesions may be less distinct. In addition, diseases that normally do not produce scarring of keratinized skin or oral mucosa can induce resorption of the labia minora, narrowing of the introitus, and scarring of the clitoral hood. Vulvar scarring can occur from any inflammatory condition.4

When examining the vulva, it is important to make sure there are no physical abnormalities, particularly, that all normal anatomy is present. Using a diagram can help and this also can be shared for patient education (Fig. 78-1). Unimpressive physical findings are sometimes associated with severe itching and vulvar pain. Lichenification manifested only by a slight change in texture can present with severe pruritus deserving of and responsive to aggressive therapy. Finally, a complete mucocutaneous examination is crucial, because extragenital findings can assist in the diagnosis of several genital conditions.

Related Physical Findings

Skin disease affecting the vulva more often has a multifactorial etiology, compared to other areas of the body. The primary skin disease is often accompanied by and driven by a secondary yeast infection, bacterial colonization, or lack of estrogen, even in the absence of obvious clinical findings. The infection can be purely cutaneous, purely vaginal, or both. Irritant contact dermatitis from topically applied agents often exacerbates both signs and symptoms. Such contributors need to be constantly sought.

Vulvar symptoms cannot be divorced from vaginal abnormalities. Irritating or infected vaginal secretions are a common cause of vestibular (introital) symptoms, which makes a speculum examination highly advisable in many instances.

Skin biopsy specimens for hematoxylin and eosin staining and direct immunofluorescence testing may be required. Sometimes multiple biopsy samples are required to establish a specific histologic diagnosis. When previously well-controlled dermatoses flare, repeat biopsy may be needed to rule out squamous cell carcinoma or a second disease process. When doing a vulvar biopsy, preanesthetizing the area with a topical anesthetic can be very helpful.

Culture of cutaneous swab samples, for Candida and bacteria, is indicated when concurrent infection is considered. Infection can complicate treatment at any point in the course of a disease.

A microscopic evaluation of vaginal smears allows inspection for yeast (see Chapter 189), Trichomonas, and bacterial vaginosis (see Chapter 205). Abnormalities such as an increased number of white blood cells or the presence of immature epithelial cells may be seen as well and may be markers for inflammatory skin diseases, estrogen deficiency, foreign body, or pyogenic bacterial infection. Vaginal cultures, done in addition, can identify infection caused by a nonalbicans Candida organism, a pathogen difficult to see on microscopic smears but occasionally a cause of significant symptoms.

Patch testing is important if allergic contact dermatitis is suspected (see Chapter 13). Consultation with specialists in gynecology, urology, or urogynecology may be necessary to assist with diagnosis, management, or treatment. This is particularly true in the setting of multifactorial processes (e.g., incontinence as a contributing factor) or diseases requiring surgical intervention (e.g., posterior fourchette fissuring).

Because of the varied morphologies and frequent multifactorial presentations, the differential diagnosis of a vulvar condition can be quite broad (Box 78-2). Normal variants can be confusing as well. The diseases discussed in this chapter are grouped into the categories of inflammatory dermatoses, bullous and erosive diseases, ulcers, abscesses, and vulvodynia.

Women with vulvovaginal symptoms assume they have a curable, infectious disease. Patients need to be counseled that many genital dermatoses are controllable but not curable. These women cannot be evaluated and treated in a 10-minute office visit; they require adequate time for education and reassurance. Frequently they need to be followed long term.

Several factors need to be considered when treating most dermatoses of the female genitalia.

Many women are unfamiliar with their genital anatomy and do not have the vocabulary to accurately discuss their problem or follow instructions for applying topical medications. Diagrams and/or a use of a hand-held mirror are extremely helpful for patient education. The vulvar diagram (Fig. 78-1) can be very important here.

An ointment is generally the most comfortable vehicle for delivering medication to the modified mucous membranes of the vulva. Ointments spread easily, require very small volumes per application, are less sensitizing and generally cause less burning.

Irritant contact dermatitis is a common complicating factor in any genital dermatosis. Aggressive washing and use of soaps, topical medications, and home remedies are the most common offenders. Because soaps, douches, disinfectants, and very hot or cold water often are not considered relevant by patients, information regarding their use is often not volunteered, and very careful questioning is warranted. Gentle cleansing of the area can be accomplished by flushing once a day with water (or mild cleanser and water) and patting dry. Washcloths for washing and towel rubbing while drying must be avoided.

Superpotent glucocorticoids such as clobetasol propionate are often required to treat dermatoses of the female genitalia. Fortunately, glucocorticoid atrophy is surprisingly uncommon on the modified mucous membranes of the vulva. Nonetheless, patients should be reevaluated monthly during periods of daily use and warned about side effects due to spread of medication to the surrounding areas where atrophy is more likely to occur such as the inguinal crease, proximal medial thighs, and perianal skin. Limit the amount of topical steroid prescribed.

Tacrolimus or pimecrolimus can be used as steroid-sparing medications on vulvar skin. Stinging or burning frequently occurs with initial application. This is especially true for very inflamed or eroded areas. These agents are often less effective than glucocorticoids and their long-term safety is still in question. Despite these issues they are a useful second line option.5 (For efficacy and side effects, see Chapter 221.)

Warmth and moisture of the genital area are unavoidable and promote infection and maceration. Bacterial superinfection can be treated with oral antibiotics. Yeast infections are especially common, particularly when patients are treated with topical glucocorticoids and/or oral antibiotics. The identification of infection on red, scaling, and often exudative skin can be difficult and should be pursued actively in patients with recalcitrant symptoms.

There is great variety in normal vulvovaginal anatomy. Vulvar and vaginal erythema of varying degrees is present in most asymptomatic premenopausal women, but this redness is rarely noticed before the onset of discomfort. Architecturally, the labia minora exhibit a wide range of asymmetry and sizes. Normal but very small labia minora may be difficult to differentiate from scarring produced by inflammatory skin disease. Sebaceous glands may be prominent on the inner labia minora. Harmless, soft, finger-like, skin-colored, monomorphous papules called vulvar papillomatosis can be seen around the hymenal ring. (See eFig. 78-1.1) These can be confused with genital warts.

Clinically subtle inflammation of the vulva sometimes produces remarkable symptoms. Therefore, a very careful examination with a high index of suspicion for a dermatosis is required.

Lichen Simplex Chronicus

(See Chapter 15)

Vulvar lichen simplex chronicus is most often seen in atopic individuals with sensitive skin. It can complicate other vulvar dermatoses, especially contact dermatitis, lichen sclerosus and, less frequently, lichen planus.

The morphologic manifestations of lichen simplex chronicus when it occurs on the vulva vary from minimal hyperpigmentation and dullness of texture of the modified mucous membranes to remarkable lichenification and edema (see Fig. 78-2 and eFigs. 78.2.1, 78.2.2, 78.2.3, 78.2.4, and 78.2.5). Erythema can be subtle on the labia majora because hair obscures the skin. Excoriations and fissures within skin folds are common but heal quickly and may not be seen in the office. Sometimes hydrated, thickened lichen simplex chronicus appears white, mimicking lichen sclerosus, or the leukoplakia of intraepithelial neoplasia.

Although the histologic findings, differential diagnosis, and therapy are similar for lichen simplex chronicus affecting the vulva as for that involving other parts of the body, there are several notable modifications.6 Contact dermatitis needs to be recognized and treated as it frequently confounds management. Women overwash and especially scrub the area and also may apply topically whatever they can find. Topical glucocorticoid therapy is a mainstay, but prompt alleviation of symptoms often requires a higher potency preparation than is standard for intertriginous skin. Those with significant lichenification do well with a superpotent preparation such as clobetasol propionate for the first few weeks. The potency or frequency can be decreased as the patient improves. Nighttime sedation is often required to interrupt the itch–scratch cycle.7 Skin and vaginal infections, often subclinical, are extremely common and often drive lichen simplex chronicus. Therefore, skin and vaginal cultures for yeast, and especially to rule out methicillin-resistant Staphylococcus aureus (MRSA), should be performed, especially since treatment will normally require potent topical glucocorticoid therapy for control. Treat bacteria and Candida infections orally because topical treatment can irritate and intensify pruritus. Proper hydration is essential for healing. Patients with lichen simplex chronicus that is intensely inflamed, excoriated, or eroded generally require medications in an ointment base, to avoid additional sensitizers and the drying effects of cream and lotion bases. A plain water soak in a tub for 5 minutes three times a day, followed by gentle patting of excess moisture and the application of a Class 3–1 corticosteroid ointment is the best approach for initial therapy, and must be done under cover of an appropriate oral antibiotic and fluconazole. Sedation is very helpful initially to stop scratching, with hydroxyzine or doxepin at night to tolerance. Systemic corticosteroids should be used for short periods of time for severe pruritus. Follow-up to prevent and manage relapse is essential.

Irritant and Allergic Contact Dermatitis

(See Chapters 48 and 13)

Vulvar skin is thin, damp, and permeable. It is exposed to a wide range of insults from washcloths and vigorous scrubbing to caustic, irritating or allergenic cleansers, and topical products applied to alleviate symptoms. Irritant vulvar dermatitis is common, ranging from the diaper dermatitis seen in infants and elderly incontinent ladies to the chapped, sore vulva of the overzealous scrubbers. Allergic vulvar contact dermatitis is less common, with relevant allergens found in 30% of those tested.8

Irritant and allergic contact dermatitis of the vulva can be either a primary or secondary diagnosis, acute or chronic. Either or both may commonly complicate any vulvar dermatosis. A patient with acute irritant contact dermatitis experiences burning on contact with the offending substance. Deep erythema is common. Vesiculation, rare, can occur on keratinized skin, whereas erosion is usual on modified mucous membranes (Fig. 78-3). Therapies such as fluorouracil, imiquimod, podophyllin resin, benzocaine, some topical antifungal creams, and topical gentian violet can produce a brisk reaction.9 Chronic irritant contact dermatitis is characterized by poorly demarcated erythema or hyperpigmentation that can be difficult to appreciate because the vulva normally is pink or dusky (eFig. 78-3.1). Lichenification and scale, when present, make diagnosis easier. Pruritus can be intense.

Although the British have found allergic contact dermatitis to be a common finding on the vulva, American physicians report few relevant positive results on patch tests for patients with eczematous vulvar skin.8–11

Nevertheless, women with refractory vulvar symptoms should be evaluated clinically and a thorough history taken to identify allergic contact dermatitis. In acute allergic contact dermatitis of the genital area, vesicles erode as quickly as they form, producing painful exudative erosions and plaques. Chronic allergic contact dermatitis is manifested more often by mild erythema and subtle edema. Notable scale is infrequent. Scratching in more severe and chronic cases induces lichenification. Common allergens include diphenhydramine, neomycin, polymyxin, sulfonamides, benzocaine, some antifungal creams, spermicides, glucocorticoids, some antiseptics, fragrances, and preservatives (see Chapter 13). As can occur with eyelid dermatitis, allergens can be carried inadvertently from fingertips to the vulva during the course of scratching or wiping. In addition, the habits of sexual partners can be important (consort dermatitis).

The therapy for vulvar contact dermatitis is the same as for this disease occurring in other areas and hinges most importantly on avoidance of irritants and allergens. Irritant, and to a lesser extent allergic, contact dermatitis can be a complicating factor in most vulvar conditions.12 It can also obscure underlying disease. Women with chronic symptoms often are well served by discontinuing all topical therapies (eFigs. 78-3.2 and 78-3.3). For a severe or extensive eruption, use systemic steroids, avoiding topicals except for a bland emollient like petrolatum. Be sure to stop all offending hygiene practices and control secondary infection and pruritus. For a mild-to-moderate eruption a Class II–IV topical steroid ointment applied twice daily can hasten improvement. Reevaluation 1 or 2 weeks later may reveal an underlying primary process.

Psoriasis

(See Chapter 18)

Vulvar psoriasis is too often missed. Women are embarrassed to mention it to their dermatologist. They show it to the gynecologist, unfamiliar with skin conditions, who cannot help with recognition and management. Dermatologists need to ask female psoriatics if they have genital rashes. Although vulvar psoriasis generally is accompanied by psoriasis in other typical locations, the vulva is a common site of Koebnerization. Vulvar psoriasis usually affects only fully keratinized skin, sparing the modified mucous membrane of the inner labia majora and the labia minora. Vulvar psoriasis typically exhibits dusky red, well-demarcated plaques. Rather than thick, silvery scale, the moistness of inverse psoriasis or a glazed, shiny surface texture is seen (Fig. 78-4, eFigs. 78-4.1, 78-4.2, and 78-4.3).

Genital psoriasis often responds well to topical therapy. A mid- or high-potency glucocorticoid ointment generally is required for significant clinical or symptomatic improvement. Calcipotriene ointment, tacrolimus ointment, or pimecrolimus cream can be tried as well, but some patients find these too irritating. For extensive psoriasis, methotrexate, oral retinoids, cyclosporine, or the newer biologics are required.

Lichen Sclerosus

(See Chapter 65)

Lichen sclerosus is the commonest cause of chronic vulvar dermatosis. The prevalence is 1:300–1:1,000. The onset is bimodal in premenarchal girls and perimenopausal women.

Clinical Findings

Lichen sclerosus begins asymptomatically in most patients. Women often tolerate their disease comfortably until they develop a superimposed complicating event, such as candidiasis or atrophic vaginitis that produces itching, followed by scratching, and the process becomes self-perpetuating. At presentation, the most common symptom of lichen sclerosus is pruritus (mild or severe). Because vulvar skin affected by lichen sclerosus is fragile, scratching often produces painful erosions. Many women, by the time they come for treatment, exhibit late signs of lichen sclerosus, including remarkable textural changes and scarring with loss of normal vulvar architecture. Scarring and narrowing of the introitus may make intercourse painful, even intolerable.

Lichen sclerosus begins with white papules or plaques that often occur first on the anterior vulva and periclitorally. Although these papules and plaques are sometimes smooth and somewhat waxy, especially when they occur on moist skin, the classic presentation is one of a hypopigmented, well-demarcated plaque with a shiny, crinkled cellophane-like surface (Fig. 78-5 and eFigs. 78-5.1, 78-5.2, 78-5.3, and 78-5.4). Generally, the skin is quite thin and fragile, with erosions and purpura being common manifestations. Some women, particularly those who experience intolerable itchiness, exhibit thickened hyperkeratotic skin with extensive secondary changes, including fissuring, crusting, and even bleeding (eFig. 78-5.5). Many patients with lichen sclerosus experience progressive scarring (eFig. 78-5.6). Resorption of the labia minora and scarring of the clitoral hood, which buries the clitoris, are common in long-standing disease (Fig. 78-6). Extragenital lichen sclerosus of keratinized skin occurs in a minority of women with vulvar lichen sclerosus and is most often located on the upper trunk and arms (see Chapter 65). Usually, extragenital lesions are asymptomatic.

An association of lichen sclerosus with circulating autoantibodies has been reported, but the only association with autoimmune disease sufficient to justify laboratory testing is with hypothyroidism.13

Differential Diagnosis

Fully developed lichen sclerosus with hypopigmentation and distinctive shiny or crinkled textural changes is easily recognized. Unfortunately, lichen sclerosus is sometimes subtle or mimics other diseases (Box 78-3).

Complications

Sexual dysfunction results from scarring and introital narrowing. Four to five percent of patients are reported to develop squamous cell carcinoma in the natural course of lichen sclerosus.4,15 Squamous cell carcinomas occurred primarily in patients with chronic hyperkeratosis or erosions. With effective topical therapy, this risk is understood to be lower.

Treatment

Although topical glucocorticoids reduce symptoms, they do not always normalize the skin texture or prevent scarring. The application of a superpotent topical preparation once or twice a day alleviates symptoms within a few days, but several months of therapy is required for resolution of the clinical findings.14,15

Most patients require 3–5 months of once- or twice-daily application to achieve maximal improvement. Patients should be followed monthly during periods of daily treatment to monitor the skin for steroid side effects and for improvement so that the frequency of application can be decreased.16 As an adjunct therapy for the first week or two to control scratching and hasten healing, sedating dosages of an antihistamine or a tricyclic antidepressant are helpful. Any infection must be controlled.

Lichen sclerosus usually is not eliminated permanently by therapy. One survey showed an 84% recurrence rate among patients off therapy.17 Despite the frequent requirement for long-term maintenance therapy, however, there is no proven optimal schedule. Most patients do well with two to three carefully localized weekly applications of a superpotent glucocorticoid on an ongoing basis.

No other treatments for lichen sclerosus produce the striking and prompt benefit of a topical superpotent glucocorticoid. Intralesional triamcinolone is used in resistant areas. In addition, other medical therapies generally have shown benefit only in open-label series. Tacrolimus and pimecrolimus (see Chapter 221) have been reported effective.18

Beneficial effects have also been described historically with topical testosterone, progesterone, and estrogen, but the benefit is minimal and equivalent to that of vehicle or lubrication alone.19–21

Topical tretinoin 0.025% and calcipotriol sometimes produce improvement, but their usefulness is limited because they can cause irritation.22,23

Oral retinoids have been reported to be helpful for some.24 The Chinese literature abounds with reports of benefit from traditional Chinese herbs and acupuncture for lichen sclerosus.25

Surgical therapies, including cryotherapy, vulvectomy, carbon dioxide laser vaporization, pulsed dye laser therapy, and photodynamic therapy have been advocated for the treatment of lichen sclerosus.26–30

Vulvar Fissures

Small, linear fissures on the vulva are common causes of itching, stinging, and dyspareunia.31 Sometimes these fissures present clinically as painful, erythematous lines in skin folds and at other times they present as obvious linear erosions.

Most well recognized are fissures at the posterior fourchette that split during intercourse (Fig. 78-7 and eFig. 78-7.1). These produce tearing pain initially, followed by burning and stinging when alkaline semen touches the area. The skin heals quickly, but splits recur with intercourse. The cause is unknown. The condition usually occurs suddenly, after years of comfortable coitus. Adequate lubrication and positioning of the woman on top can minimize tearing. Otherwise, surgical excision (perineoplasty) is required, with the vertical fissure excised and the skin closed front to back with advancement of the vaginal mucosa to cover the area.32

Recurrent fissuring within skin folds, especially in the interlabial sulci of the vulva, is a common cause of stinging and irritation of the vulva. Women typically complain of a sensation of “paper cuts.” Intercourse and tight clothing are often precipitating events. Isolated acute fissuring is associated most often with Candida colonization or infection. Skin fold fissures can result from any inflammatory dermatosis, including psoriasis, lichen sclerosus, and lichen simplex chronicus. When one of these factors is identified, treatment is directed toward its correction. When no specific underlying cause is found, a topical glucocorticoid ointment combined with an oral antibiotic and anticandidal medication often eliminates the fissuring. However, almost immediate recurrence is common, and prolonged therapy may be required to break the cycle.

Lichen Planus

(See Chapter 26)

Vulvovaginal lichen planus is much less common than vulvar lichen sclerosus with a likely prevalence of 1 in 2,500–4,500. It is often misdiagnosed as lichen sclerosus.33

Clinical Findings

Vulvovaginal lichen planus has a wide variety of clinical manifestations. Erosive vulvovaginal lichen planus is most common and is generally very symptomatic. It presents with burning, rawness, and dyspareunia with variable itching. Nonerosive lichen planus of the vulva may appear bland with mainly itching and irritation, but it can be very symptomatic and be accompanied by serious accompanying erosive vaginal disease. Irritating inflammatory vaginal secretions can produce symptoms of introital burning and stinging. Disease may be restricted to the vagina with no vulvar manifestations. Rectal and perianal disease is common and often produces pain.

White, lacy, reticulate striae resembling papular oral lichen planus sometimes occur on the modified mucous membranes of the vulva (Fig. 78-8 and eFig. 78-8.1). Less easily recognized are solid, uniformly hypopigmented, flat white plaques that mimic lichen sclerosus except for the absence of crinkled cellophane paper-like texture (eFig. 78-8.2). Erosive lichen planus is manifested by a glazed erythema and variable red, painful erosions that are either nonspecific or surrounded by typical white, often scalloped, epithelial changes (eFigs. 78-8.3 and 78-8.4). Erosive vulvovaginal lichen planus is often accompanied by erosive buccal and gingival oral disease.34,35

Lichen planus, especially when erosive, produces remarkable scarring (eFig. 78-8.5). Resorption of the labia minora and obliteration of the clitoris under an agglutinated clitoral hood are very common. Narrowing of the introitus occurs more often and more severely than with lichen sclerosus, and vaginal adhesions can close the vagina, preventing both intercourse and introduction of a speculum (eFig. 78-8.6).

Vaginal erosions are often obvious, appearing as bright red, often raw, patches, but sometimes equally painful disease can be subtle and show only mild erythema on a speculum examination. Scarring may vary from a minor synechia, slight narrowing or vaginal shortening to vaginal obliteration. Vaginal discharge can be light to heavy and bloody. An examination of vaginal smears is a sensitive test for the presence of vaginal inflammation. Large, flat, cuboidal, mature desquamated vaginal epithelial cells are replaced by smaller, rounded basal cells shed from erosions and rapidly proliferative inflamed vaginal epithelium and sheets of leukocytes are seen. Up to 77% of patients with oral lichen planus have vulvovaginal lichen planus, but are often unaware and should be examined for asymptomatic involvement.36,37

The diagnosis of lichen planus is made either by biopsy or by the identification of classic lacy lesions in association with other typical mucous membrane lesions. Biopsies are often nonspecific and a negative biopsy does not rule out this diagnosis.

Differential Diagnosis

When lichen planus presents classically and involves oral and genital mucosa, it is easy to diagnose. Unfortunately, lichen planus on the vulva alone can be indistinguishable from other diseases (Box 78-4).

Complications

The inflammation, pain, and scarring commonly cause sexual dysfunction, and at times, anger and depression. Vulvar squamous cell carcinoma has been well described in patients with erosive genital lichen planus. The magnitude of this risk is not known, but patients should be evaluated for this condition regularly.

Treatment

The aggressive treatment of vaginal lichen planus is crucial for patient comfort. Meticulous local care with early treatment of infection, minimization of external irritants, and attention to any underlying atrophy of estrogen deficiency are important measures. A vaginal dilator should be used daily to prevent adhesions of the vaginal walls. Emotional support and careful patient education regarding the nature of the disease, its prognosis, and its therapy are vital.

Pruritic, noneroded vulvar lichen planus is usually quite well managed simply by the application of a potent topical glucocorticoid ointment. Severe erosive vulvovaginal lichen planus can present a difficult therapeutic problem. A superpotent glucocorticoid ointment applied to the vulva is standard first-line therapy. For mild-to-moderate disease, a gram of the glucocorticoid ointment can be inserted into the vagina as well, or hydrocortisone acetate 25 mg rectal suppositories can be inserted nightly into the vagina.38

For severe disease, use a compounded 100-mg/g hydrocortisone acetate vaginal cream, 3–5 g nightly for 2 weeks, decreasing to three times a week as maintenance. Systemic steroids are also used and the least toxic is deep intramuscular triamcinolone 1 mg/kg up to 80 mg/dose. This may be repeated monthly for 3 months and limited to four doses per year (personal experience). Patients are warned about adrenal suppression and given fluconazole 150 mg weekly to prevent candidiasis. Any patient with vulvar disease receiving an intravaginal glucocorticoid should be told of her increased risk for yeast infection. There is little tendency for erosive vulvovaginal lichen planus to remit, but it can be well controlled. The severity tends to wax and wane, sometimes as a result of secondary infections, exposure to irritants, or stress but more often for no identifiable cause. Bursts of oral predniso(lo)ne or intramuscular triamcinolone can be helpful for flares.

Topical tacrolimus and pimecrolimus have been reported to be useful in the treatment of vulvar lichen planus, but these medications are irritating.39,40 They can be used as “steroid sparers” once the inflammation is controlled.

Other medications that have been reported primarily in open trials as useful for the treatment of erosive mucous membrane lichen planus include hydroxychloroquine, methotrexate, retinoids, azathioprine, cyclophosphamide, mycophenolate mofetil, and thalidomide.41–45

Erythema Multiforme Major, Stevens–Johnson Syndrome, and Toxic Epidermal Necrolysis

(See Chapters 39 and 40)

Erythema multiforme major, Stevens–Johnson syndrome, and toxic epidermal necrolysis all lead to erosive vulvar disease. One retrospective survey of 40 women with toxic epidermal necrolysis revealed that 28 had vulvovaginal involvement with severe erosions, of whom five experienced permanent scarring.46 These patients were unable to engage in intercourse, even after corrective surgery. Local care during the serious phase of the illness can prevent long-term dysfunction due to scarring. Prompt treatment of secondary bacterial or Candida infection may be important. In addition, daily insertion of a vaginal dilator (such as an inexpensive syringe cover) is important to ensure patency.

Cicatricial Pemphigoid

(See Chapter 57)

Cicatricial pemphigoid regularly produces multiple mucosal erosions. The nonspecific, painful erosions of the vulva and surrounding epithelium can be clinically indistinguishable from lichen planus and lichen sclerosus. Vulvar erosions generally are accompanied by nonspecific vaginal erosions that can result in significant vaginal scarring. Management consists of both local glucocorticoid therapy and systemic treatments.47 Vaginal treatment is the same as for erosive vaginal lichen planus. Again, local care, the use of vaginal dilators, and secondary infection control are important factors in management.

Pemphigus Vulgaris

(See Chapter 54)

Pemphigus vulgaris often presents with mucosal erosions on the vulva. Although pemphigus vulgaris is usually considered to be a nonscarring disease, vulvovaginal involvement can lead to scarring, with vaginal adhesions and obliteration of vulvar architecture. As with cicatricial pemphigoid, a high index of suspicion and confirmatory biopsies are important in reaching the correct diagnosis. For treatment, see Chapter 54.

Fixed Drug Eruption

(See Chapter 41)

Erosions due to fixed drug eruption sometimes occur on the vulva. Common offenders include acetaminophen, hydrochlorothiazide, nonsteroidal anti-inflammatory medications, oral contraceptives, sulfa drugs, penicillin, tetracyclines, allopurinol, barbiturates, and furosemide.48,49 Lesions are most often located in the vestibule or on the modified mucous membranes of the labia minora or medial labia majora. Unlike the classic, round, edematous plaques or blisters seen on keratinized skin, the erosions of a fixed drug eruption on the vulva are often irregular, sometimes with a slightly shaggy border. Often there are one or a few typical lesions on keratinized skin, or there are oral erosions. The deepening hyperpigmentation seen on keratinized skin affected by recurrent fixed drug eruptions is usually absent on the modified mucous membranes of the vulva (eFig. 78-8.7 and eFig. 78-8.8).

Herpes Simplex

(See Chapter 193)

Extramammary Paget Disease

(See Chapter 121)

Vulvar Carcinoma

(See Chapters 113 and 114)

Aphthae

(See Chapters 76 and 166)

Aphthae, “canker sores,” common in the oral cavity, are often misdiagnosed on the vulva where they occur more frequently than the few literature reports would suggest. These are acute, painful ulcers that can be single or multiple (Fig. 78-9).

They typically affect girls 9–19 years of age and present with the sudden onset of painful, punched-out, well-demarcated vulvar ulcers, usually less than a centimeter (range 0.5–5 cm). The ulcers are most often found on the vulvar trigone, the labia, and less frequently the lower vagina. Typically there is a prodrome with flu-like symptoms of mild fever, headache, and malaise. There may be a past history of oral aphthae. The ulcers last 1–3 weeks and resolve. Scarring is variable. Usually there is just one episode but these can recur. The pathogenesis probably involves the interaction of genetic factors with infection as a trigger. The hypothesis is that microbial antigens with molecular mimicry induce a reactive process directed at host antigens. Commonly the antigenic agent is unknown, but a number of cases have been associated with Epstein–Barr virus, a few cases with Mycoplasma pneumoniae, HIV, or cytomegalovirus50–52 (eFig. 78-9.1 and 78-9.2). The combination of recurrent oral plus genital ulcers is complex aphthosis.53 This pattern is seen most commonly with inflammatory bowel disease, Crohn disease and ulcerative colitis and, less commonly with, celiac disease. It also can occur infrequently with medications, myeloproliferative diseases, neutropenia, lymphopenia, and some rare syndromes like FAPA syndrome (fever, aphthae, pharyngitis, and adenitis). Rarely, in North America, these ulcers are associated with Behçet's disease. This is a frequent association in the Middle East.

Diagnosis is one of exclusion. Biopsies are often taken but are usually nonspecific. For acute ulcers, test for Herpes simplex, sexually transmitted diseases including HIV, Epstein–Barr virus, and Mycoplasma. For chronic recurrent ulcers investigate for inflammatory bowel disease and the less common causes above. The differential diagnosis includes herpes simplex, other sexually transmitted infections (syphilis, chancroid), and pyoderma gangrenosum.

A short course of prednisone is best for acute disease. For recurrent aphthae, colchicine, dapsone, colchicine combined with dapsone, cyclosporine, and thalidomide have been used.53

Crohn Disease

(See Chapter 150)

Crohn disease is a noninfectious granulomatous inflammatory disorder that primarily involves the bowel, but vulvar and perianal skin are sometimes affected. Vulvar involvement is underrecognized and misdiagnosed.54 Only 55 cases are reported in the literature, but most vulvar specialists have managed vulvar Crohn cases.

The average age is 34 years. Metastatic spread is the most common presentation (91%). Symptoms include swelling (62%) and pain (20%). Examination usually shows swelling and induration in the labia majora with or without ulcers that extend to the groin. The ulcers occur in 41% and can be the classic “knife-cut” type in the skin folds, aphthous ulcers, or both55 (Fig. 78-10 and eFigs. 78-10.1, 78-10.2, and 78-10.3).

The diagnosis is made on the basis of biopsy results and identification of the bowel disease, but 25% of vulvar Crohn disease patients have no gastrointestinal symptoms. The primary disease to be differentiated from anogenital Crohn disease is hidradenitis suppurativa (see Section “Hidradenitis Suppurativa”), which is said to coexist in 17% of cases of Crohn disease. Other diseases to rule out are sarcoidosis, tuberculosis, lymphogranuloma venereum, and atypical pyogenic infections. Treatment is with systemic therapy for the underlying intestinal Crohn disease.56,57

Topical and intralesional glucocorticoids and local care can help to induce healing of ulcerations.

Syphilis

(See Chapter 200)

Chancroid

(See Chapter 202)

Other Ulcerations in Sexually Transmitted Diseases

(See Chapters 203 and 204)

Abscesses occur in Crohn disease (see Section “Crohn Disease”), gonorrhea (see Chapter 205), hidradenitis suppurativa (see Section “Hidradenitis Suppurativa”), and Bartholin gland (see below).

Bartholin's Cyst and Abscesses

The Bartholin's glands are the largest of the vulvar vestibular glands. They secrete mucus-like material for lubrication during sexual activity. Cysts form due to occlusion of the opening ducts. They are located on the lower labia minora at 5 and 7 o'clock just lateral to the hymenal ring. Cysts can range from 1–3 cm in size and are often asymptomatic.58

Diagnosis is clinical with the typical nodule of varying size lying in the posterior vestibule with the labium minus classically “transecting” the cyst (Fig. 78-11). No treatment is necessary for asymptomatic Bartholin's cysts unless the patient is over 40 and there is concern about carcinoma.

Bartholin's duct abscesses develop as an infected obstruction of the Bartholin's duct. Infection is typically from Escherichia coli, Staphylococcus, or Streptococcus.59,60 Occasionally, it is a sexually transmitted infection. Patients present with severe pain and swelling and sometimes an inability to sit or walk. The cyst is warm, swollen, and tender with a varying degree of surrounding edema and erythema. Treatment is with incision and drainage and for complicated infections appropriate antibiotics. Recurrent lesions require specific surgery.

Hidradenitis Suppurativa

(See Chapter 85)

Hidradenitis suppurativa is a chronic, inflammatory, recurrent, debilitating, follicular disorder predisposed to involve intertriginous areas.61–64 It presents with painful, deep seated, inflamed lesions, note that the newest classification makes no mention of apocrine gland involvement.

The Second International Hidradenitis Suppurativa Research Symposium (San Francisco; March, 2009) adopted the following diagnostic criteria that must be met to establish the diagnosis:

1. Typical lesions—i.e., deep-seated painful nodules: blind boils in early lesions; abscesses, draining sinuses, scars, and “tombstone” open comedones in secondary lesions.

2. Typical topography—i.e., axillary, groin, perineal and perianal lesion, buttocks, infra and intermammary folds.

3. Chronicity and recurrence.

Most commonly the axillary, inguinal, inframammary, and anogenital regions. This disease is more common in women than men, with a ratio of 3.3 to 1 and affects 1% of the general population. It is frequently misdiagnosed as “boils,” delaying diagnosis, and leading to fragmented care and progression to a chronic, disabling condition that has a profoundly negative impact on quality of life.62 Onset is usually in a woman's twenties with remission after menopause. The course varies from intermittent and benign to continuous and severe.

In women these “boils” present classically in the groin and around the hair-bearing areas of the vulva, less often on the modified mucous membranes, but commonly in the axillae and under the breasts (Fig. 78-12).

The nodules can be extremely painful nodules and very debilitating. Rupture and drainage of malodorous purulent material can be very distressing. Lesions vary from a few acneform nodules that last 7–15 days to persistent chronic hypertrophic scars, with dense fibrosis forming linear rope-like bands with varying degrees of drainage from interconnecting sinuses. In more severe cases, hidradenitis suppurativa results in chronic erosions from draining ulcerations and lymphedema from lymphatic obstruction. It can be difficult to differentiate from Crohn disease and they can coexist.65

The Second International Hidradenitis Suppurativa Research Symposium (San Francisco; March, 2009) adopted the following diagnostic criteria that must be met to establish the diagnosis:

1. Typical lesions—i.e., deep-seated painful nodules: blind boils in early lesions; abscesses, draining sinuses, scars, and “tombstone” open comedones in secondary lesions.

2. Typical topography—i.e., axillary, groin, perineal and perianal lesion, buttocks, infra and intermammary folds.

3. Chronicity and recurrence.

Treatment depends on severity, using the Hurley classification.66

At all stages, if appropriate, androgen blockade with nonandrogenic birth control pills, spironolactone, and/or finasteride are used.67 Smoking must cease. All friction or trauma to the areas of involvement must be avoided. Oral zinc has been used as an anti-inflammatory.68

Stage I (Abscess Formation Without Sinus Tracts)

Treatment is aimed at reducing flares using topical clindamycin lotion, courses of antibiotics for 7–10 days (tetracycline, doxycycline, clindamycin), oral zinc gluconate, and intralesional triamcinolone or a short oral course of predniso(lo)ne. Low-dose isotretinoin is useful in a minority of cases.69

Stage II (Recurrent Abscesses with Sinus Tracts and Scarring, Single or Multiple Widely Separated Lesions)

(eFig. 78-12.1).

Management requires the above medical therapy as baseline plus surgical treatment to reduce activity to Stage I and also to prepare for wide unroofing of sinuses and persistent cysts. Antibiotics such as the tetracyclines or clindamycin and rifampicin are used in combination for 3 months.70,71 At times dapsone may be helpful. Intralesional triamcinolone and short courses of predniso(lo)ne are used to quickly control swelling and inflammation.

Stage III (Diffuse or Extensive Involvement, or Multiple Interconnecting Tracts and Abscesses Across the Entire Area)

This is a surgical disease. Medical treatment is essential in preparation for surgery.72 Anti-inflammatories may be necessary. The biologics can provide dramatic preoperative improvement but are not a cure.73,74

Surgical management need not be heroic and widely ablative in Stage II and early Stage III. The preferred technique is to unroof the sinuses as early as possible, to include a thorough exploration and exposure of any secondary sinuses and cysts, and then eradicate to the extent possible inflammatory masses responsible for perpetuating the lateral extension of lesions.75,76

Vulvodynia is chronic vulvar pain with no identifiable cause. Vulvar pain is a challenging problem for caregivers and, too often, a very difficult problem for women. Pain can seriously impact their lives, affecting not only their sexuality but also their daily activities, even what they can wear. Vulvar pain and vulvodynia have been defined and classified by the International Society for the Study of Vulvovaginal Disease.77 (Box 78-5). Vulvodynia is defined as vulvar pain in the absence of relevant, visible physical findings or a specific clinically identifiable neurological disorder. All vulvar pain conditions due to specific disorders, infections, inflammatory disorders, neoplastic conditions, or neurological conditions must be excluded.78–80

Vulvodynia is divided into localized (formerly vulvar vestibulitis) (eFig. 78-12.2) and generalized (formerly dysesthetic vulvodynia). Both of these groups can be further divided into those who experience provoked (brought on by touch), unprovoked (spontaneous), or mixed (both provoked and unprovoked) pain. Localized vulvodynia can be primary as in pain present with first tampon use or vaginal entry, or secondary, as in acquired after some years of no pain on touching/vaginal entry.

Epidemiology

Unexplained vulvar pain is highly prevalent among women of reproductive age with lifetime prevalence estimates ranging from 16%–28%. The prevalence of true vulvodynia is unknown because careful clinical evaluation is required for a definitive diagnosis.3,81,82 Localized provoked vulvodynia usually affects younger women and is more common than generalized vulvodynia.83

Etiology and Pathogenesis

The etiology of vulvodynia is unclear. It is likely multifactorial with both organic and functional components. Etiological factors being studied range from neuropathic mechanisms, neural hyperplasia, neurogenic inflammation, abnormal nociception, and neurotransmitter and neuropeptides anomalies, to pelvic floor muscle dysfunction. There are localized processes in the vulva that can trigger pain and changes centrally in the dorsal root ganglia and in the brain, changes that keep the pain active. The result is abnormal pain perception so that light touch causes pain (allodynia).

More work has been done on localized vulvodynia. Patients are overly sensitive to pain and cannot downregulate it. They have increased nerve fibers, inflammatory cells, and mediators in the vulvar vestibule along with a poor ability to modify pain. The pelvic floor muscles are dysfunctional, tight, and weak, and play an important role in causation or perpetuation (and are not just a consequence) of vulvodynia. Underlying psychosexual issues or personality traits, such as somatization disorder, can be important.84 Depression and anxiety have been reported. These patients may have other comorbid hypersensitivity syndromes with centralized pain such as migraines, irritable bowel syndrome, and fibromyalgia.85,86 Very few studies have looked at generalized vulvodynia, and it may represent pudendal neuralgia or a regional pain syndrome.

Clinical Findings

Patients with localized vulvodynia are usually between the ages of 20–50. Typically there is pain on touch or attempted vaginal entry (referred to as provoked pain). This may be with the first use of a tampon or sexual intercourse (primary vulvodynia) or after years of no discomfort (secondary vulvodynia). The patient complains of burning, stinging, irritation, or a raw sensation at the vaginal entrance (hymenal ring area).87–89 The pain can be moderate-to-severe. Sexual intercourse is difficult to impossible. They may complain of constant vaginal infections despite negative tests or that their partner is too big. They are often distressed, anxious, and/or depressed. Patients with generalized vulvodynia, usually over 40 years old, have constant or episodic vulvar pain. They complain of burning, soreness, rawness, stabbing pain, irritation, aching, or stinging, but they usually can have sexual intercourse. They are hyperaware of their genital area. They often complain of “constant yeast.” These patients have often seen many caregivers, had multiple incorrect diagnoses, and tried many treatments.

On examination there is no visible abnormality. The pelvic floor muscles may be tight and sensitive. Q-tip sensitivity (see below) may be prominent in localized vulvodynia.

Differential Diagnosis

The diagnosis of vulvodynia is one of exclusion. The diagnosis of localized vulvodynia is made on history and the demonstration of pain on Q-tip touching around the hymenal ring. Patients with vulvodynia should be examined carefully for any underlying skin disease, infection, neoplasm, or well-defined neurologic disorder. Irritant contact dermatitis, vulvar fissures, and lichen planus are the most common skin diseases to be mistaken for vulvodynia. Painful vaginitis from nonalbicans Candida infection or a noninfectious inflammatory vaginitis (desquamative inflammatory vaginitis) can be confused with vulvodynia. Desquamative inflammatory vaginitis is manifested by grossly and microscopically purulent vaginal secretions and immature epithelial cells similar to those seen in lichen planus. Nonalbicans Candida infections, such as C. glabrata, C. krusei, and Saccharomyces cerevisiae infection also can cause chronic vulvovaginal pain. These infections are easily missed unless a culture is performed, and they can be resistant to therapy. Finally, neurologic disorders such as postherpetic neuralgia, pudendal nerve entrapment, pudendal neuralgia, and spinal compression need to be addressed through history and imaging studies when appropriate.

Treatment

Vulvodynia is complex, and with multiple possible contributing factors many medical/surgical, psychological, and alternate approaches have been used. The different aspects of vulvodynia therapy are ideally addressed simultaneously using a multidisciplinary approach.

Education and support are vital. There are excellent resources through the National Vulvodynia Association (http://www.nva.org).

All irritating hygiene practices must stop. Good education here is needed to avoid laundry detergents, cleansers, pads, ill-fitting clothing, etc., that could cause local harm. Activities that hurt, like bike riding, must stop. Sexual intercourse should be avoided when there is pain.

For topical pain control lidocaine 5% ointment has decreased pain up to 50%. Topical 6% compounded gabapentin cream has been helpful for over 50% of generalized vulvodynia patients. Topical estradiol cream has been used for cases of localized vulvodynia. Other local treatments with a few reports include topical capsaicin, and local injections (as pain blocks) using lidocaine with methylprednisolone.

Systemic medications are often used as pain modulators. Tricyclic antidepressants such as amitriptyline or desipramine, beginning at very low dosages and increasing up to 150 mg or until the patient is comfortable, are first-line.90 For women who do not tolerate tricyclic antidepressants or who experience suboptimal improvement, gabapentin has been used.91 The newer antidepressants venlafaxine and duloxetine have been used effectively as well. Pregabalin provides yet another possible option. Combinations of these medications can be used.

Pelvic floor dysfunction needs to be addressed with the help of a pelvic floor physiotherapist who can also assess the back and hips to make sure no other confounding biomechanical problems are present. Treatments to normalize pelvic floor function include myofascial release, trigger-point pressure, biofeedback, vaginal dilation, and exercises.

Attention to depression and sexual dysfunction is mandatory. Most patients benefit from referral for counseling to help them cope with their debilitating symptoms. Behavior and cognitive-behavior therapy can reduce the fear of pain and improve sexual functioning with good results.

For localized vulvodynia, surgical vestibulectomy has been successful in over 60% of cases. It is best for secondary vulvodynia, especially when combined with pelvic floor therapy. It is usually chosen only when conservative treatment fails.

For generalized vulvodynia with neuralgia, management in a pain clinic using nerve blocks and interventional devices (sacral nerve root stimulators) may be needed.

However, improvement is usually slow and trial-and-error therapy with support by the physician is required.85,86,83,92,93

Pruritus vulvae is common, affecting perhaps 10% of women. It can be acute or chronic, minor, or debilitating. The most common cause is candidiasis. Irritant contact dermatitis is next, due to overwashing and topical irritants, particularly urine, feces, and sweat, as well as various topical medications.

The commonest chronic vulvar conditions are lichen simplex chronicus and lichen sclerosus and, less frequently, lichen planus and psoriasis. Often there is a combination of infection, contact dermatitis, and one or more dermatoses. Rarely the problem is due to a neuropathy or underlying malignancy. Investigation and treatment is directed at the individual causes. It is always important to eliminate all irritants and control infection. Sedation to stop scratching is often imperative. Topical or at times systemic corticosteroids can be very effective for inflammation. The calcineurin inhibitors can be used as “steroid sparers.”

There is a group of women in whom it is very difficult to pinpoint a cause for the itching. The majority of these have some degree of neuropathy with or without anxiety or depression. Treatment is with neurotropic agents as used for vulvodynia; anxiety andor depression must be addressed.94–96