Both chronic infections and benign tumors, most commonly condylomata acuminata, appear white because keratin absorbs moisture, which reflects light back to the observer.

To avoid the ambiguous term leukoplakia, Jeffcoate, in 1966, introduced the term dystrophy into the nomenclature of benign epithelial lesions of the vulva. Predictions about the malignant potential of vulvar dystrophy vary; of all the types of dystrophy, the one most often benign is lichen sclerosus. As noted earlier, the terminology for vulvar dystrophies has been altered. Vulvar dystrophy has been classified in three categories: squamous hyperplasia, lichen sclerosus, and VIN. Typical squamous cell hyperplasia is characterized by a thickened, hyperkeratotic squamous epithelium, elongated rete pegs, and often an infiltration of the underlying tissue with chronic inflammatory cells. Typical hyperplasia is a benign form of chronic dermatitis with hyperkeratosis and acanthosis; thus, the designation “dystrophy” should be eliminated.

Leukoderma and vitiligo are terms that are used interchangeably. Treatment is not required unless the symptoms of the commonly associated chronic dermatitis cannot be controlled by local medications. The hyperkeratotic lesions comprise a number of diverse entities that share a white to grayish white epithelial appearance in a moist environment. Biopsy is the only reliable criterion for accurate assessment.

Lichen sclerosus is characterized by hyperkeratosis, thinning of the epidermis, loss of rete peg architecture, collagenization of the underlying tissue, and associated middermal inflammatory infiltrate (Fig. 23.2). In 2006, the ISSVD classified lichen

sclerosis as lichenoid pattern. It can occur at any age. The disease has been noted in the prepubertal child, and it occurs during the menstrual years. Nevertheless, it is seen most often in the postmenopausal woman when the lesions more commonly are symptomatic, perhaps because of the additional epithelial compromise caused by atrophy. The genetic aspects of lichen sclerosus have not been clearly identified, but the finding of lesions in both mother and child has been documented.

If biopsy specimens reveal lichen sclerosus, the patient should be treated with ultrapotent corticosteroids. Many series over the past few years have shown an excellent clinical response to 0.05% clobetasol proportionate topical ointment or cream. In a series of 81 women with biopsy-proven lichen sclerosus, Lorenz and coworkers reported that 77% had complete remission of symptoms and another 18% experienced significant improvement. Patients were treated with topical application of clobetasol cream twice daily for 1 month, at bedtime for another month, and, finally, twice a week for 3 months. They continued to use the cream on an “as-needed” basis once or twice a week. Many patients continue to require occasional episodic therapy for symptomatic flareups, but the long-term effects of these ultrapotent steroids on the vulva have not been well studied. Some experts recommend maintenance therapy with lower potency corticosteroids, such as triamcinolone or 0.1% betamethasone. Topical testosterone has been recommended in the past, but Bornstein and associates compared the results of 2% testosterone propionate with 0.05% clobetasol dipropionate; at 1-year follow-up, 80% of the clobetasol-treated patients reported symptomatic improvement compared with 40% of those treated with testosterone.

Many patients with chronic vulvar dermatitis, stenosis of the outlet specifically related to lichen sclerosus, and vestibulitis have an associated constriction of the vaginal outlet with resultant dyspareunia. Local intravaginal or vulvar applications of estrogen do not improve this condition. Plastic surgery to the outlet (Fig. 23.3) may be helpful. By excising a triangular area of skin beneath the fourchette, the surgeon can undermine and evert the adjacent vaginal epithelium, incise the transverse perineal muscle and fascia, and cover the denuded area with a flap of vaginal mucosa. The procedure is simple, and the use of delayed absorbable suture material lessens the incidence of wound breakdown that commonly occurs when absorbable suture is used. The results of this procedure have been most satisfactory; approximately 95% of patients are greatly relieved of dyspareunia. Breech and Laufer have reported good results in a few patients by suturing a protective covering of oxidized regenerated cellulose gauze (Surgicel, Johnson & Johnson, Arlington, TX) to the raw surfaces of the inner labia and clitoris after division of intracoital adhesions to prevent recurrence.

Biopsy with a Keyes punch can be performed in the office with the use of local anesthesia. Knife biopsies often are tangential and contain only the superficial layers, which results in a less than accurate histologic interpretation. An alternative is to use a cervical biopsy forceps to obtain a small specimen that can be evaluated. Correct orientation of the tissue in the fixative is mandatory if accurate evaluation of the specimen is to be rendered. Such orientation can be obtained by placing the biopsy specimen on filter paper or Telfa with the epithelial surface exposed, so that the pathologist can embed the specimen accurately. Tangential cutting may result in the erroneous diagnosis of invasive disease. Cytology has not proved to be a satisfactory screening technique in the evaluation of the precursory cellular atypias in vulvar neoplasia.

The classic bowenoid changes vary from one microscopic section to another, but typical sections show loss of polarity, hyperchromasia, anaplasia, individual cell keratinization, corps ronds, and mitotic activity on the surface (Fig. 23.6). Abnormal mitosis may abound. Other gross variations include the erythroplastic lesion (erythroplasia of Queyrat) with immature cells extending from base to surface and lesions that appear almost normal, being marked only by intraepithelial pearl formation at the rete tips in a background of marked dysplasia. Papillary lesions showing changes of high-grade dysplasia were previously designated as bowenoid papulosis, a term discontinued by ISSVD.

Although surgical excision of VIN is favored, patients typically do not require total vulvectomy. Modesitt and colleagues found invasive cancer in 22% of patients with biopsies consistent with VIN III. Vulvectomy may be appropriate for selected patients who are elderly, particularly if they have extensive disease, or for patients with Paget disease. Wide local excision usually is successful, but an attempt should be made to
obtain clear margins. The adjacent loose skin of the vulva provides sufficient extra skin to cover minor defects without a skin graft and without significant deformity. The incidence of recurrence is no greater with local excision than with total vulvectomy, but it still approaches 30% to 40%. Positive margins have been indicative of an increased risk of recurrence in some series. Unless invasive cancer is suspected in the area of the positive margins, immediate reexcision is usually not indicated, but careful follow-up is necessary because recurrence is common. Brown has suggested that CO₂ laser vaporization around the surgical margins will decrease the risk of recurrence.

A skinning vulvectomy, in which the epidermis and underlying dermis of the vulva and often the perineal area are removed and replaced by a skin graft, has been used for the treatment of extensive or multifocal vulvar in situ disease. This procedure is usually recommended in younger women with extensive lesions in an attempt to restore normal anatomy and sexual function. However, the technique requires surgery at a donor site, which produces an additional scar in a patient who usually is young. Furthermore, it imposes prolonged bed rest, near-complete immobilization of the lower extremities, and indwelling bladder catheterization for 5 to 6 days while the skin graft heals.

The carbon dioxide laser has been successfully used in the treatment of in situ vulvar neoplasia. This approach is of particular appeal for the younger patient with multifocal, viral proliferative disease. This subset of patients with VIN is undoubtedly at lower risk for occult invasion. Emphasis in therapy should be directed toward preservation of maximum tissue and vulvar function. Given these considerations and the reality of recurrences, laser ablation provides an effective medium. Pretreatment requirements include careful examination of the lower genital tract and the liberal use of biopsies to identify areas of possible invasion and multicentric disease. The risk of invasive cancer is greater in the older patient. The desire for cosmetic results is less, so the use of surgical excision is favored in older women.

The laser itself is directed colposcopically after examination of tissues prepared by the application of dilute acetic acid. The latter may enhance detection of minimal viral changes not readily seen with the naked eye. Although benign condylomata can be adequately treated by superficial vaporization (so-called first and second plane), laser treatment of VIN must address the extension of disease into the hair follicles (pilosebaceous ducts). This mandates deeper laser vaporization beyond the papillary dermis and into the upper reticular dermis (third plane). The colposcope permits recognition of landmarks that characterize these levels. Baggish and coworkers identified skin appendage involvement in 36% of cases of vulvar in situ carcinoma and predicted that laser vaporization to a depth of 2.5 mm would effectively treat involved appendages in 95% of cases. Shatz and associates advocated ablation of VIN to a depth of 1 to 2 mm in nonhairy and hairy skin to achieve similar success. In laser treatment of VIN, the use of appropriate power densities should be emphasized. Low-power densities lead to thermal conduction injury in adjacent and underlying normal tissue. The latter increases the risk of scarring. Power densities of greater than 750 W/cm² are recommended. However, the deeper extent of vaporization required for VIN III, particularly in hair-bearing areas of the vulva, results in considerably greater postoperative pain, a longer period of healing, and an increased risk of scarring and subsequent chronic pain and dyspareunia; therefore, many experts have abandoned the use of the laser in favor of surgical excision for VIN III. Bornstein and Kaufman have proposed combining laser ablation with surgical excision in the treatment of selected patients with VIN. Laser is used particularly in areas where excision hampers preservation of anatomy, such as in the clitoral region. Laser therapy for VIN should probably be reserved for experienced laser surgeons and colposcopists.

The ultrasonic surgical aspirator can assist the surgeon in ablating to depths comparable to those achieved with the CO₂ laser. The advantage of this instrument is its ability to obtain additional tissue that might identify an occult cancer. Ultrasonic surgical aspirator and laser ablation also may be used to treat perianal intraepithelial neoplasia. In this setting, two concerns should be kept in mind. This location appears to be associated with a greater risk for the development of invasive squamous cancer, and the likelihood of fibrosis, scarring, and stricture is heightened. As with all treatments for VIN, the potential for recurrence and the need for further follow-up must be appreciated. With ablative approaches such as laser, diligence must be exercised to exclude invasion.

Topical agents have been used in the treatment of VIN with inconsistent results. Most notable among these topical treatments has been 5-fluorouracil (5-FU, Efudex 5%). Efudex is not recommended by the manufacturer for this use, and they specifically recommend against its use in the vagina. The mechanism of action appears to be related to the inhibition of DNA and RNA synthesis; the latter is not specific to dysplastic or HPVinfected cells. Normal epithelium is susceptible to the agent, and a component of hypersensitivity reaction appears operative in its mode of action. For cases in which treatment is effective, denudation of the epithelium is a requisite for success. This understandably leads to localized discomfort and pain, often reported as intense burning. Treatment regimens with topical 5-FU are diverse, and no standardized administration protocol has been widely adopted. One technique is topical application on an alternate-night basis for as long as 6 weeks; patient compliance problems typically lead to earlier curtailment. Among young patients with erythroplastic VIN, a 50% to 60% complete response rate has been reported. The hyperkeratotic VIN lesion has not proved to be as responsive to 5-FU.

In a 41-year review of 405 women, Jones and colleagues observed that more than 50% of women treated with laser ablation or surgical resection required an additional procedure within 14 years. Fifty percent of patients with positive surgical margins required additional treatment within 5 years. In comparison with positive margins, women with negative margins had a 15% chance of requiring additional therapy. Brown and colleagues, in a small series of 33 patients, noted a decrease in recurrence with a combination of surgical excision and laser vaporization at the margins.

Topical agents have been effective in treating vulvar pruritus and should be tried initially. When they are ineffective, often, it is secondary to their inability to penetrate the thickened hyperkeratotic surface. Initially, treatment for a specific disease should be instituted. For example, topical steroids should be used for psoriasis, antifungals for candidiasis, and appropriate ablative therapy for molluscum contagiosum and condylomata acuminata. Vulvar dermatoses such as lichen sclerosus, lichen simplex chronicus, lichen planus, seborrheic dermatitis, and plasma cell vulvitis can be effectively treated with highpotency topical steroids such as betamethasone. Many of these patients also present with vulvar dysesthesia (vulvar burning) and can be treated with tricyclic medications such as amitriptyline and nortriptyline.

For historic purposes, no chapter on vulvar pruritus would be complete without mentioning alcohol injection and the Mering procedure. Before treatment with amitriptyline became popular, patients with recalcitrant pruritus and vulvar dysesthesia were treated with local alcohol injection. The anogenital area was prepped and draped in a sterile manner after the induction of general or regional anesthesia. The region was then divided into 1-cm squares with a marking pen of brilliant green. Absolute alcohol, 0.2 mL, was then injected subcutaneously at the intersection of these lines (Fig. 23.8). Postoperatively, the patients were treated with cold packs and cool sitz baths for 1 week.

Because of the effectiveness of topical high-potency steroid creams, the Mering procedure is rarely used to treat vulvar pruritus in the United States today. It requires hospitalization and careful surgical technique (Fig. 23.9). The skin is shaved and thoroughly cleaned, and the incision is outlined with a marking pencil. The incision is made on the outer surface of the labium majus. It extends to the fascia of the urogenital diaphragm from the level of the clitoris to slightly beyond the fourchette and may continue inferiorly to the level of the anal orifice, depending on the extent of the pruritus. The nerves in the adjacent tissue are severed with a finger placed on each side, moving from the lateral aspect of the clitoris toward the midline, over the clitoris, where the fingers meet. The procedure interrupts branches of the ilioinguinal and genitofemoral nerves (Fig. 23.10). Blunt dissection extends posteriorly to the lateral side of the rectum, outside the external anal sphincter. If the perianal area is involved, blunt dissection may extend to the posterior limit of the anal orifice, where the two fingers meet behind the anus in the midline breaking up the branches of the pudendal nerve.

It is important that hemostasis be meticulously maintained. A small, flat Jackson-Pratt drain should be placed under the flap on each side. The subcutaneous tissue is approximated with absorbable sutures, and the skin is sutured with polyglycolic acid or polyglactin 910 material. The area must be packed tightly for 24 hours, and the patient should use ice packs or cool tub baths. Domeboro sitz baths (Burow solution) may help to relieve edema.

A careful diagnostic evaluation is essential because of the apparent multifactorial etiology of vestibulodynia. If an infectious etiology is present, it is imperative to treat it. Recombinant alpha-interferon is efficacious in treating vulvodynia with a history of condylomata acuminata or subclinical HPV. Triamcinolone acetonide 0.1% and bupivacaine can also be injected monthly. An alternative combination is methylprednisolone and lidocaine submucosal.

Chronic recurrent candidiasis is treated with prolonged oral administration of ketoconazole or fluconazole. Topical anticandidal regimens should be prescribed when oral antifungal medications are discontinued.

In addition to being treated for the infectious etiology, all patients should be started on a course of topical steroids. Horowitz treats all patients with vulvodynia with hydrocortisone acetate 1% or 2.5% with 1% pramoxine hydrochloride ointment (Pramosone) for 2 to 3 months. After 3 months of this therapy, the patients are placed on desoximetasone 0.25% ointment (Topicort). Only after failing topical steroids are the patients considered for surgical treatment. Oral amitriptyline is also an important part of the therapeutic regimen. Doses of 25 to 75 mg taken 3 hours before bedtime are prescribed. Patients with vulva dysesthesia or interstitial cystitis benefit most from medical therapy with amitriptyline. Oral gabapentin is also helpful in some patients. It should be started with a gradual dose escalation and tapered off when discontinued.

Carbon dioxide laser ablation of the vestibular glands has not been shown to be optimal and has resulted in scarring and increased dyspareunia in some patients. In 1995, Reid and associates reported long-term results with the flashlampexcited dye laser in nonresponders to medical therapy. Those with poor responses to laser vaporization were then treated with gland resection. Overall response rates were 62% to 80%, depending on the distribution of tenderness. However, long-term follow-up has been disappointing, and this approach remains controversial.

Primary surgical therapy has produced relief of symptoms in 75% to 90% of patients. This technique was initially described by Woodruff and associates in 1981 and Friedrich in 1987 and was modified by Marinoff and Turner in 1991 to include the periurethral Skene gland openings. The outer incision extends circumferentially from the periurethral glands along Hart line to the contralateral glands. The proximal vaginal margin is just inside the hymenal ring. This horseshoe-shaped epithelium is superficially excised and sent for histologic diagnosis. In almost all cases, the histology consists of nonspecific periglandular chronic inflammation, much less impressive than might be expected based on the severe symptoms reported. As in a perineoplasty, the vaginal mucosa is undermined and the vagina advanced to approximate edges. The wound is closed in two interrupted layers of 3-0 polyglactin 910 (Vicryl) or polyglycolic acid (Dexon) sutures (Fig. 23.12). Postoperative treatment is the same as for perineoplasty. Coitus should be avoided for 2 to 3 months after surgery.