Women's Sexual Function and Dysfunction. Irwin Goldstein MD

Overview of vulvar pain: pain related to a specific disorder and lesion-free pain

Lynette J Margesson, Elizabeth Gunther Stewart


Vulvar pain and dyspareunia have been mysterious entities for many years, regarded until the mid-1980s as psychosexual in origin.1 In 1983, the term “vulvodynia” was adopted by the International Society for the Study of Vulvovaginal Disease, sparking efforts to identify pathology. The US National Institutes of Health-sponsored conferences on vulvodynia in 1997 and in 2003 brought insights into the neurobiology of pain. Researchers at the Karolinska Institute in Sweden identified differences in the vestibule of women with pain compared with pain-free individuals. Drug companies have begun active efforts to develop medication that targets vulvo- dynia


Contrary to early suggestions that it is rare, chronic unexplained vulvar pain is a highly prevalent disorder. In a 2003 National Institutes of Health-sponsored study of 4915 women, 16% reported chronic burning, knifelike pain, or pain on vulvar contact that lasted for at least 3 months.2 Similar findings have been reported on a Web-based survey.3 In a 2002 survey of 1094 American women, 288 (27.9%) reported pain at the vulvar vestibule, 80 (7.8%) reporting pain within the past 6 months, 31 (3%) reporting pain that lasted 3 or more months, and 18 (1.7%) reporting vestibular pain lasting 3 or more months that occurred within the past 6 months.


The latest classification of vulvar pain agreed upon at the October 2003 Congress of the International Society for the Study of Vulvovaginal Disease4 included two major headings: (1) vulvar pain related to a specific disorder and (2) vulvodynia. The first of these was subdivided as follows:

1. Infectious (candidiasis, herpes, etc.)

2. Inflammatory (erosive lichen planus, immunobullous disease, etc.)

3. Neoplastic (Paget’s disease, squamous cell carcinoma, etc.)

4. Neurologic (herpes simplex and post-herpetic neuralgia, spinal nerve compression, etc.).

Vulvodynia was defined as “vulvar discomfort, most often described as burning pain, occurring in the absence of a relevant specific infectious, inflammatory, neoplastic, or neurologic disorder, either

1. Generalized, involving the whole vulva

(a) provoked (sexual contact, nonsexual contact, or both),

(b) unprovoke (spontaneous),

(c) mixed (provoked and unprovoked), or

2. Localized, involving a portion or component of the vulva such as the vestibule, clitoris, hemivulva, or other specified site: vestibulodynia, clitorodynia, hemivulvodynia, etc.,

(a) provoked (sexual contact, nonsexual contact, or both),

(b) unprovoked (spontaneous),

(c) mixed (provoked and unprovoked).”

Until the pathophysiology of pain is completely worked out, the definitions will continue to evolve. This chapter, fundamental to diagnosis of pain underlying female sexual dysfunction, covers essential material on common specific disorders as well as lesion-free causes of vulvar pain.

Vulvar pain related to a specific disorder


Herpes simplex virus infection

General description

Worldwide, herpes simplex virus is the commonest cause of vulvar ulceration and pain. Typically, it is characterized by recurrent painful outbreaks of grouped vesicles and erosions. The etiology is usually herpes simplex virus type II (80% of cases) and less commonly herpes simplex virus type I, although in some areas type I is becoming more prevalent. Primary herpes simplex virus infection is not commonly seen. Most patients have had unrecognized primary herpes simplex virus infection, and they present with nonprimary, recurrent disease.5 Ninety per cent of herpes simplex virus II-positive women carriers are unaware of their infection. Up to 80% of women with herpes simplex virus II mistakenly think their symptoms are due to such things as vaginitis, soap allergy, poor lubrication, clothing irritation, urinary infection, or vaginitis. They are often shocked to find that their recurrent, variable, sore or painful vulvar problem is herpes simplex virus. The transmission usually is sexual, occurring during periods of asymptomatic viral shedding. Most affected individuals are unaware they are infectious.

Clinical features

Characteristic symptoms of primary disease are paresthesia, fever, malaise, headache, and myalgia. Pain varies from mild to deep, boring, and severe. Dysuria is common. Episodic itching, irritation, and burning signal recurrences. Women are often totally unaware of recurring herpes simplex virus.

In primary disease, there are often extensive groups of vesicles or pustules with surrounding redness and swelling (Fig. 12.2.1). These break, leaving tender erosions and ulcers that last 1-2 weeks. With primary herpes simplex virus, there can be large, impressive, painful ulcers (Fig. 12.2.2). Recurrent herpes simplex virus shows limited, scattered vesicles, pustules, and erosions that last 5-7 days (Figs 12.2.3 and 12.2.4). Less commonly, and often misdiagnosed, there are fissures or “pimples”. Recurrent episodes of vulvar burning and itching with no skin signs can occur - herpes sine eruptione.6,7


Herpes simplex virus culture is the reference standard if positive, but false negatives are common. Type-specific serology is used to distinguish between herpes simplex virus I and herpes simplex virus II infection.5,9

Figure 12.2.3. Typical recurrent herpes simplex with small painful erosions.


General description

Infection of the vulva and/or vagina by Candida albicans occurs once during their lives in 75% of women, 40-45% have more than one episode, and 5% have recurrent candidiasis, over four episodes yearly.11 Candida albicans causes over 85% of cases.12

Candida pathogenesis involves colonization, and then transformation to symptomatic disease. Asymptomatic colonization does not require treatment. Major host factors facilitating transformation are antibiotic use, diabetes, sexual activity, and, possibly, dietary carbohydrate excess.13 While the role of reproductive hormones remains unclear,14 exogenous estrogens from oral contraceptive pills and hormone therapy, or local estrogen is believed to contribute.15 Candidiasis often complicates dermatoses and topical steroid use.

Figure 12.2.4. Severe, painful, recurrent herpes simplex showing swelling and erosion of the labia minora with pustules seen on left inner labium majus.

Clinical description

Signs and symptoms of vulvovaginal candidiasis include a whitish, cheesy discharge with pruritus, irritation, soreness, dyspareunia, and dysuria. Erythema and fissuring may be seen (Figs 12.2.5 and 12.2.6). Burning is often a feature of pathogens other than C. albicans. No sign or symptom, individually or collectively, is pathognomonic.16 Candidiasis can occur with low-grade symptoms and without discharge.

Diagnosis cannot be made by history and physical examination alone.17 Microscopy and pH are essential, and since microscopy is only 40% specific, culture is imperative if yeast is not seen. Unfortunately, the diagnosis is made daily in thousands of women on the basis of a telephone conversation or noninclusive physical examination. Many other factors may account for identical signs and symptoms; hence, the need for laboratory confirmation is critical. Self-diagnosis is poor.18 Other mimicking conditions include physiologic discharge, vestibulodynia, contact or irritant dermatitis, vulvovaginal atrophy, lichen sclerosus or lichen planus, and desquamative inflammatory vaginitis.


One must first rule out other sexually transmitted diseases. For primary herpes simplex virus infections, local or oral analgesics and cool soaks can help. Specific oral antiviral treatment is indicated with valacyclovir 1 g twice a day for seven to ten days or famciclovir 250 mg three times a day for seven to ten days. For recurrent herpes simplex virus infection use valacyclovir 500 mg twice a day for three to five days or 1 g once daily for five days or famciclovir 125 mg twice a day for five days. To suppress herpes simplex virus infection use valacyclovir 1 g daily or famciclovir 250 mg twice a day. The length of suppressive therapy varies and needs to be evaluated yearly.

Figure 12.2.5. Vulvar candidiasis with diffuse erythema, swelling, and fissures.

Figure 12.2.6. Close-up of the painful fissures in Fig. 12.2.5.


Trichomoniasis is diagnosed by microscopy of vaginal secretions with visualization of motile, ovoid, flagellated organisms. This method is 60-70% sensitive; backup culture is important if suspicion is high. Polymerase chain reaction testing has an 84% sensitivity24 but is not approved by the US Food and Drug Administration.

Treatment of trichomoniasis with metronidazole 2 g orally as a single dose or 500 mg orally for 7 days has cure rates of 90-95%. Treating sex partners is encouraged. Vaginal gel is less efficacious; no other therapy is approved by the Food and Drug Administration. About 5% of cases are estimated to be resistant; most can be treated with increasing doses of metronidazole 500 mg b.i.d. for 7 days, or 2 g daily for 3-5 days.25 Guidance from the Centers for Disease Control and Prevention is available for difficult cases.

To facilitate treatment, candidiasis is classified.17 Uncomplicated cases include mild to moderate severity, infrequent outbreaks, in a normal, nonpregnant host, showing pseudohyphae of C. albicans on microscopy. Complicated cases are moderate to severe, recur four or more times a year, can be non-C. albicans, and occur in an immunocompromised, diabetic, or pregnant host. Recurrence may also represent inadequately treated infection.19 Ninety per cent of the patients who seek treatment for candidiasis have uncomplicated disease, treated with short-course therapy with a topical azole agent or a single 150-mg dose of fluconazole. Prolonged therapy necessary for complicated candidiasis includes two doses of 150-mg fluconazole 72 h apart, or 150 mg weekly for 6 months.20

Non-C. albicans yeasts, such as C. glabrata, respond poorly to azoles. They are treated with boric acid (600 mg) inserted vaginally nightly for 14 days.21


General description

Vaginal infection with Trichomonas vaginalis is the most common sexually transmitted infection worldwide.22 In the USA, trichomoniasis is second to chlamydia in estimated annual incidence. The protozoan is associated with sexual intercourse and is not generally spread by fomites. It frequently occurs with bacterial vaginosis and gonorrhea in women of all ages.

Trichomoniasis is no longer regarded as simply annoying, but may be associated with adverse pregnancy outcomes such as premature rupture of the membranes and preterm delivery.23 It is also associated with increased human immunodeficiency virus (HIV) transmission.13

Clinical description

Trichomoniasis manifests as malodorous, profuse yellow-green discharge with vulvar pruritus and burning, but asymptomatic infection also can occur. If untreated, symptoms can persist for years.

Herpes zoster

General description

Herpes zoster (shingles) is an acute, painful blistering disease of the nerves of the skin and associated tissues. It usually affects one or two dermatomes and is caused by the varicella-zoster virus, another herpes virus. This virus lies latent in dorsal root ganglia after earlier varicella (chickenpox) infection. The virus is reactivated when immune surveillance is diminished by age, neoplasia, pharmacologic immunosuppression, or human immunodeficiency virus/acquired immunodeficiency syndrome.

Clinical features

With the onset of vulvar herpes zoster, pain and/or paresthesia are typically felt along the S3 dermatome. This occurs 1-5 days before the vesicular rash. Symptoms include a prodrome of headache, fever, and malaise. Before the eruption, there is usually pain, and as the pustules break, there is burning and dysuria. The involved skin is red and swollen with crops of grouped vesicles that become pustules and progress to crusted and/or open erosions (Figs 12.2.7-12.2.9). The pain can be severe. The course is 2-3 weeks. A debilitating postherpetic neuralgia, especially in the elderly, may follow, lasting months or years. 26-29


Usually the diagnosis is made clinically. Serologic testing or skin swab for direct immunofluorescence testing is available


The treatment is valacyclovir 1 g t.i.d. for 7 days; famciclovir 500 mg t.i.d. for 7 days. Pain control is very important. For postherpetic neuralgia, treatment with tricyclic antidepressants, gabapentin, and oxycodone is effective. Start a tricyclic such as amitriptyline or nortriptyline in a low, gradually increasing dose (10 up to 50-75 mg) in older patients, as they are the ones at risk of postherpetic neuralgia. These drugs should be started immediately along with antiviral medications. Help from a pain clinic may be needed.29-31

Epstein-Barr virus

General description

Epstein-Barr virus is another herpes virus. Classically, it causes infectious mononucleosis. Occasionally, acute painful vulvar ulcers are seen in teenagers and young adults.

Clinical features

There may be a prodrome of fever, malaise, sore throat, mouth ulcers, and enlarged cervical glands. In the vulva, there is an acute onset of pain, burning, and dysuria with punched-out, red- rimmed, single or multiple, vulvar ulcers (Fig. 12.2.10). These last 1-2 weeks and resolve with no scarring. They are often mistaken for herpes simplex virus infection, but all tests for the latter are negative.


The diagnosis of Epstein-Barr virus (EBV) is made with specific serology testing for the antibody to viral capsid antigen for EBV on both acute and convalescent serum (the MonoSpot test may be negative).


Only symptomatic treatment is needed.

Inflammatory disease

Lichen planus

General description

Lichen planus is a relatively common, lymphocyte-mediated, inflammatory, mucocutaneous dermatosis. Usually, it affects the oral cavity and skin, but it can involve the vulva and vagina in 5% of cases. This involvement is referred to as the vulvovaginal-gingival syndrome or erosive or ulcerative lichen planus. It can affect not only skin and mucous membranes but also ears, eyes, esophagus, bladder, and anus. The vulvovaginal disease may be in isolation or part of a more widespread eruption. It is of uncertain etiology but evidence supports an autoimmune, T-cell-mediated condition triggered by an exogenous antigenic stimulus. Erosive lichen planus can cause significant pain, dyspareunia, and apareunia. It may be self-limited, but the erosive form can be very chronic.

Figure 12.2.10. Severely painful ulcers right labium minus from Epstein-Barr virus infection.

Clinical features

The typical patient is 30-60 years of age. There may be few to no symptoms, just variable itching and irritation. With the eroded and ulcerative form, symptoms are more severe with pain and dysfunction. Pain and burning are the main complaints and the physical findings often are missed, as they can be subtle or poorly recognized. With vaginal involvement, there can be complaints of dyspareunia, apareunia, and purulent, malodorous discharge. On physical examination, there may be a whitish, gray, lacy reticulated pattern on the vulvar mucous membranes (Fig. 12.2.11) with secondary excoriations or even thickening due to scratching. In the painful erosive form, there is redness with partial or full-thickness erosions showing a gray or whitish edge (Fig. 12.2.12). The erosions are glossy red and classically present around the labia minora and vestibule. Normal architecture is lost, with destruction of labia minora and clitoris. Scarring causes synechiae on the vulva and in the vagina. The introitus may be stenosed. The vagina can become friable, atrophic, shortened, scarred, or even obliterated. Signs of lichen planus can be seen elsewhere, particularly the oral cavity, which may show the reticulated lacy pattern or even ulcers (Fig. 12.2.13). On the body is a purple to red, polygonal, itchy, papular, and sometimes scaling rash.

Figure 12.2.11. Painful, eroded vulvar lichen planus involving the clitoris and periclitoral areas. Note typical white, lacey pattern and scarring around the clitoris.


Diagnosis can be made on the clinical pattern in the genital area, mouth, and skin. Biopsies should be examined with routine histopathology and direct immunofluorescence.


Treatment is challenging. There is no single, universally effective treatment. All irritation to the area must stop. All infections (such as yeast) must be managed. Corticosteroids are the mainstay, being used as ointment, vaginal cream, or foam or systemically. Superpotent topical corticosteroid, halobetasol, or clobetasol 0.05% ointment, is usually chosen for primary treatment. Systemic steroids then may be required if there is no response.

Anecdotally reported treatments include hydroxychloroquine, cyclosporine, systemic retinoids, tetracyclines, dapsone, azathioprine, and methotrexate.

Surgery may be required for vaginal adhesions or in reconstruction of the vagina, although the success rate for these procedures is disappointing. There is a small risk of malignancy. These patients need long-term supervision with a lot of support, which is best done with a multidisciplinary team.

Figure 12.2.12. Severely painful vulvar lichen planus with glazed erythema and scarring plus loss of labia minora and most of clitoris.

Lichen sclerosus

General description

Lichen sclerosus is a common inflammatory mucocutaneous disorder of the vulva that presents with itching and/or irritation. Whiteness, thinning, and scarring changes are seen. Less commonly, there is pain, usually due to secondary factors. The definitive etiology is unknown, but most likely this is a multifactorial, autoimmune, familial condition. Family history is positive in 22% of patients, and up to 44% have various autoantibodies. The age of onset is 35-45 years of age, but children as young as 1k years have been affected. Squamous cell carcinoma of the vulva develops in 3-4% of these patients.

Clinical features

The clinical picture is variable. Pruritus is the commonest complaint, usually with a mixture of itching, burning and dyspareu- nia. At times it is asymptomatic. Pain and burning may be the main, primary complaint. Usually pain is associated with open areas or fissures due to infection (bacteria and yeast), contactants (irritant or allergen), trauma (scratching or intercourse) or tumor (squamous cell carcinoma). Signs of lichen sclerosus range from the typical white, cellophane-surfaced (Fig. 12.2.14) shiny papules and scarred plaques to open erosions with secondary changes of purpura, ulcers, excoriation, lichenifica- tion, fissuring and crusting (Figs 12.2.15 and 12.2.16). There can be significant flattening of the normal vulvar architecture and scarring with loss of clitoris and labia minora and even introital stenosis. Involvement may form a figure of eight from the periclitoral area through the perineum to the perianal area.


The diagnosis is made clinically and confirmed with biopsy. Treatment43-49

The mainstay of treatment is topical superpotent corticosteroids, clobetasol, or halobetasol 0.05% ointment. These are used for 3 months and then maintenance is one to three times a week. All irritating factors must be removed. This condition can be well controlled long-term but it is seldom “cured”. Longterm follow-up is needed. Good patient education is imperative. Surgery may be necessary for dysfunctional scarring. Although the risk of malignancy is small, yearly follow-up is needed.

Figure 12.2.16. Scarring in the interlabial sulcus, clitoral area, and labia minora with painful erythema around the labium majus due to irritant contact dermatitis complicating vulvar lichen planus.

Lichen simplex chronicus


Lichen simplex chronicus is also called neurodermatitis, hyperplastic dystrophy, and squamous cell hyperplasia.

General description

Lichen simplex chronicus is the end stage of the itch-scratch- itch cycle. It is usually part of the atopic dermatitis spectrum. This is the chronic, localized, lichenified (thickened) form of atopic dermatitis. Less commonly, it is associated with secondarily scratched psoriasis or contact dermatitis. Sometimes it is referred to as the “itch that rashes”. This condition is defined by relentless pruritus but can be very painful when there are open eroded areas.

Clinical features

All patients present with a history of itching and scratching. Often they have had years of uncontrolled “chronic itch” that is worse with heat, stress, and menstruation. They have seen multiple practitioners and “nothing helps”. At night, they wake up scratching. They try anything to get relief. The end result can be open, eroded areas with pain and chronic burning.

On examination, the vulvar skin is thickened with increased skin markings termed “lichenification”. This thick, grayish skin develops due to chronic rubbing, like callused skin areas elsewhere. The involvement may be unilateral or bilateral with dyspigmentation (either hypo- or hyper-pigmentation or a combination), redness, excoriations, and variable serosan- guineous crusts and fissures (Figs 12.2.17 and 12.2.18). Although this occurs anywhere in the perineum, the labia majora are most commonly involved. There may be hair loss from scratching. Lichen simplex chronicus can complicate other skin conditions. Look for psoriasis, candidiasis, lichen sclerosus, lichen planus, and contact dermatitis.

Secondary factors are often a problem and are the main cause of pain and burning. Infection from bacteria (usually streptococcus or staphylococcus) and/or yeast may develop. Irritant contact dermatitis is very common, as these patients resort to various caustic products to relieve itch. Allergic contact dermatitis may develop. The erosions, fissures, and ulcers associated with these infections and/or topical contactants can result in severe burning pain.


This is a clinical diagnosis. Once the condition is quieter, a biopsy to look for underlying conditions can be helpful. A biopsy in the acute stage will show only secondary changes.

Figure 12.2.17. Thickened (lichenified) inner labia majora with excoriations and painful fissuring in vulvar lichen simplex chronicus.

Figure 12.2.18. Close-up of Fig. 12.2.17 with tiny painful fissures at the base of the left labium majus and excoriations on the perineum.


Identify the underlying disease. Culture for yeast and bacteria. Stop all irritants and consider referral for patch testing to rule out an allergic contactant. Restore the skin barrier function with sitz baths and no cleansers. Follow this with an emollient such as plain petrolatum or vegetable oil to hold moisture in the skin. Reduce inflammation with superpotent steroids, halobetasol, or clobetasol 0.05% ointment b.i.d. for 2 weeks, once a day for 2 weeks, and then Monday-Wednesday-Friday for 2 weeks. Treat bacterial infections with 1 week of cephalosporin, and yeast infections with at least two doses a week of fluconazole 150 mg. Stop the itch-scratch-itch cycle with doxepin or hydroxyzine 25-100 mg at night, and in the morning add citalopram 20-40 mg or fluoxetine. Always look for multiple problems, such as contact dermatitis, lichen simplex chronicus, lichen sclerosus, and infection.



Aphthae are also known as canker sores or complex aphthosis.

General description

Aphthous ulcers of the vulva are rare but very painful. Oral aphthae are common, with a lifetime incidence of 50%. Although these conditions do not occur concomitantly, they can be associated in the same individual and are referred to as complex aphthosis. Vulvar aphthae can be associated with inflammatory bowel disease such as Crohn’s disease, or myeloproliferative diseases. They can be associated with cytotoxic drugs and some syndromes such as mouth and genital ulcers with inflamed cartilage and histiocytic necrotizing lymphadenitis.

Clinical features

Vulvar aphthous ulcers are painful, punched-out, round to irregularly outlined, red-based ulcers of sudden onset that may be single or multiple. They can occur anywhere on the vulva (Figs 12.2.19 and 12.2.20). They are often 1-2 cm in diameter and heal, perhaps with scarring, over 2-4 weeks. Dysuria is common. Recurrences are common at variable intervals. Systemic complaints are often minimal.


This is a diagnosis of exclusion. Rule out, with appropriate serology, herpes simplex virus, Epstein-Barr virus, syphilis, and human immunodeficiency virus. Rule out chancroid with biopsy. Check on any possible precipitating drugs (particularly cytotoxic ones). Look for any association such as Behçet’s disease, inflammatory bowel disease, and myeloproliferative disease or syndromes as above.

Treatment5 61

Corticosteroids are the first line of treatment. Topical superpo- tent halobetasol or clobetasol 0.05% ointment twice a day can be used. For resistant aphthae, intralesional triamcinolone acetonide 3.3 to 5 mg per mL can be injected with a 30 g needle into the base of the ulcer(s). For more difficult cases oral prednisone may be needed. For recurrent disease colchicine or avlo- sulfon are used. Colchicine 0.6 mg tablets, two to three daily is recommended or avlosulfon (Dapsone) 150-100 mg per day. Some cases require both these drugs together. For severe resistant disease, thalidomide may be needed.

Contact dermatitis

General description

Contact dermatitis is an inflammation of the skin from an external agent that acts either as an irritant or an allergen, producing a rash that can be acute, subacute, or chronic. It can be irritant or allergic. Primary irritant contact dermatitis is due to the caustic or irritating effects of a substance on the skin. It develops after prolonged or repeated exposure to substances such as soap, urine, and feces - especially after over-zealous hygiene practices such as scrubbing. There is no immune reaction with this. Irritant contact dermatitis is more common on the vulva because vulvar skin is thin with a weaker barrier function. Patients with low estrogen, due to menopause, birth control pills, or giving birth have further thinning of the vulvar and vaginal tissue. Other risk factors include rashes such as lichen sclerosus or psoriasis. Incontinence of urine or feces (a very common problem in older women) and regular wearing of pads (that macerate and rub the skin) can cause further problems. To deal with their incontinence-related hygiene issues, some women compensate by washing and adding more topicals, compounding the burning and risking further incontinence-related sensitization.

Figure 12.2.19. Deep, painful, punched-out vulvar aphthous ulcers in a teenager.

Figure 12.2.20. Same patient as in Fig. 12.2.19 with recurrent, but in this case less dramatically painful aphthous ulcers. All investigation, serology, and cultures repeatedly negative.

Allergic contact dermatitis is caused by an allergy to a low dose of a chemical substance such as perfume, antibiotics (neomycin), or benzocaine, or poison ivy. This is a type IV, delayed-hypersensitivity reaction.

Clinical features

There are complaints of variable amounts of itching, burning, and irritation. Pain is not common unless there are open ulcers or erosions. The onset is slower for irritant contact dermatitis, as repeated exposure is necessary. Allergic contact dermatitis reactions are usually itchy with sudden onset with redness, swelling and, rarely in the vulva, vesiculation (Figs 12.2.21 and 12.2.22). More commonly, there is a chronic subacute pattern with dryness, scaling and redness (Fig. 12.2.23). Secondary changes such as scratching and thickening (lichenification) may be seen. Infection or a frank lichen simplex chronicus can occur. There may be a contact dermatitis superimposed on previous skin conditions such as psoriasis or lichen sclerosus.


The diagnosis is usually clinical. A biopsy may be necessary. To find an allergic etiology, thorough patch testing by a dermatologist or allergist is needed.


Identify and stop all offending agents and practices. Patients should have lukewarm to cool soaks or sitz baths daily. Replace estrogen as indicated. Give topical corticosteroid, clobetasol, or halobetasol 0.05% ointment b.i.d. for 5-7 days, and then once a day for 5-7 days and a topical bland emollient such as petrolatum or vegetable oil. Night-time sedation with hydroxyzine or doxepin, as in lichen simplex chronicus, may be necessary. If the disease is severe, give oral prednisone tapering over 14 days or intramuscular triamcinolone 1 mg/kg. Treat secondary infection.

Squamous cell neoplasia

Squamous cell neoplasms of the vulva are classified by degree of invasiveness, either intraepithelial or invasive squamous cell carcinoma.

Figure 12.2.21. Severe painful swelling, erosions, and redness of the vulva due to contact dermatitis from benzocaine.

Figure 12.2.22. Another case of benzocaine allergy with severe painful erosions and swelling.

Vulvar intraepithelial neoplasia

General description

There are two different vulvar intraepithelial neoplasia patterns: (1) multifocal, human papilloma virus associated, occurring in women aged 20-50 years, and (2) the solitary lesions that occur in women aged 60-70 years.

Clinical description

Multifocal papules or small plaques are variably colored and may be isolated or involve the vulva extensively. The solitary lesion is a single, sharply marginated pink or reddish patch or plaque (Fig. 12.2.24). Lesions may be asymptomatic, or itchy and irritated. If fissuring occurs, the lesion becomes painful.


This is a biopsy diagnosis. The disorganized histologic pattern of the epidermis in vulvar intraepithelial neoplasia shows variations in degree of dysplasia, cellular atypia, and mitotic activity. It is ranked from mild to severe.

Figure 12.2.23. Swelling and redness due to contact dermatitis of the vulva from neomycin.


Depending on the location and extent of the lesions, treatment is by excision or destruction. Topical imiquimod (Aldara) cream 5% shows promise in the treatment of vulvar intraepithelial neoplasia.68

Invasive squamous cell carcinoma

General and clinical description

Invasive vulvar carcinoma occurs as a solitary lesion on the vulva in women older than 55 years. The lesion is usually asymptomatic but if exophytic, fissured, or ulcerated, it may bleed, or become pruritic, sore, or painful (Fig. 12.2.25). Squamous cell carcinoma may occur in the background of lichen planus; 4-96% of vulvar carcinomas are associated with surrounding lichen sclerosus, depending on the thoroughness of examination of the specimen.69

Figure 12.2.24. Painful, superficial ulcer of right lower labium minus with hyperpigmented perineal plaque in vulvar intraepithelial neoplasia (VIN III). Note scarring of lichen sclerosus periclitorally.

Diagnosis is by biopsy.

Treatment requires a gynecologic oncologist to stage and remove the tumor.

Neurologic conditions

Postherpetic neuralgia

Herpes zoster infection, or shingles, is caused by the clinical recurrence of varicella zoster virus that has been dormant in sensory ganglia. The infection causes postherpetic neuralgia in 10-34% of infected patients. Neuralgia is a debilitating neuropathic pain state that persists for 1-3 months after the resolution of the herpes zoster rash. Usually, the patients are older persons, and 70% are over 50 years of age. More than 50% of patients over 60 years of age with herpes zoster develop postherpetic neuralgia due to an age-related decline in varicella zoster- specific T-cell-mediated immunity. It also occurs for the same reasons in the immunosuppressed, e.g. those with HIV infection, chemotherapeutic suppression, or cancer. Postherpetic neuralgia is more common in women (65%) than in men (35%). The lumbosacral nerves are affected in 15% of cases of herpes zoster. Vulvar shingles probably affects 1.5 million American women in their lifetime, and 150 000 have postherpetic neuralgia.70-74

Figure 12.2.25. Painful ulcerated periclitoral squamous cell carcinoma in a case of vulvar lichen sclerosus.

After the initial outbreak of herpes zoster, there is a variable pattern of neuropathic pain. It may follow a continuum with the original acute pain or a relapsing and remitting pattern, or a pain-free period may occur after the infection, and then persistent pain.

The pain is described usually as severe, excruciating, debilitating, and incapacitating. There is constant aching and burning in the vulva and perineum with jabbing, lancinating, and shooting pain. The hallmarks of postherpetic neuralgia are allo- dynia (pain triggered by non-noxious stimuli, such as clothes and light touch) and hyperalgesia (exaggerated pain response to mild noxious stimuli). These occur in 70-90% of postherpetic neuralgia. Abnormal sensations of paresthesia (“pins and needles”) and dysesthesia (other generally unpleasant abnormal sensations) also occur. Less commonly, there can be an incapacitating itch as the main feature - neuropathic pruritus. The discomfort may be continuous or intermittent day to day. Typically, it is worse with stress and fatigue - and fatigue worsens with continuing loss of sleep. It is very debilitating for elderly patients. The majority have resolution of pain in 12 months. Some patients are left with long-term, debilitating neuropathic pain.70,73-77

The most difficult patients are those who present generalized vulvodynia with all the hallmarks of allodynia, hyperalgesia, and dysesthesia, and no good history of antecedent infection. Their skin lesions may have been minor or there may have been no cutaneous findings.

Diagnosis is usually clinical with neuralgia as part of the original herpes zoster infection. Scraping of skin for direct immunofluorescence can be helpful with a turnaround time of 24 h. Viral serology may be necessary for diagnosis.


Vulvar herpes zoster in elderly women should be treated as an emergency with proper diagnosis and immediate treatment with antiviral and pain medication.

 For neuropathic pain, local anesthesia with 5% lidocaine gel is given.

 Tricyclic antidepressants, amitriptyline, or nortriptyline, provide 47-67% of patients with moderate to excellent response. It is recommended that these medications be started at the onset of the acute infection. The initial dose is 10 mg, slowly increased up to a maximum of 150 mg. Medication is given at night.

 Gabapentin is useful, starting at 100 mg and building up rapidly to three times a day and then to a total dose of 2600-3600 mg per day depending on the patient’s age.

 Opiates such as morphine and oxycodone may be necessary.

Lesion-free causes of vulvar pain

Localized vulvodynia (vestibulodynia)

General description

Vestibulodynia is unprovoked pain in the vestibule; pain on touch at the vaginal vestibule with first tampon, pelvic examination, or intercourse (primary vestibulodynia), or after a period of comfort with these activities (secondary vestibulodynia). Vestibulodynia is recognized as the most common cause of dyspareunia in the woman under 50 years.81 The dyspareunia of vestibulodynia can be psychosexually devastating.

The etiology of vestibulodynia is unknown. Theories proposed include abnormalities of embryologic development,82 increased urinary oxalate excretion,83 genetic/immune factors,84 hormonal factors,85 and Candida.86 Human papilloma virus, long suspected, is not proven by recent studies.87

The role of inflammation in vestibulodynia is widely debated; currently, the term “vestibulitis” has been replaced by vestibulodynia in the International Society for the Study of Vulvovaginal Disease terminology, since some studies found a lack of association between excised tissue and inflammation. Nevertheless, the lack of a single common risk factor in vestibulodynia points to the common denominator of vulvar inflammation or trauma as the postulated initial event that releases a cascade of inflammatory cytokines.88 This results in combined peripheral nerve sensitization and central sensitization, leading to the characteristic alterations in mechanical, thermal, and deep pressure pain threshold of vestibulodynia.89 A genetic factor may operate susceptible individuals.90

Clinical description

Women are convinced that they have recurrent yeast infection, or that they are “too small” for comfortable sexual relations. Clinicians diagnose repeated infections, or dismiss the pain as psychologic. Women with vestibulodynia meet Friedrich’s criteria, as follows:91

1. Severe pain on vestibular touch or attempted vaginal entry

2. Tenderness localized within the vestibule

3. Physical findings of erythema of various degrees.

Diagnosis is achieved by history and exclusion of vulvar pain related to a specific disorder. The distinct differences in pain response to light touch to the vestibule permit a clear, reliable diagnosis of vestibulodynia92 by the Q-tip test. A moistened, cotton-tipped swab is used to touch around the vestibular “clock” (see Chapters 9.5 and 12.1); painful areas may be focal or diffuse.

A myriad of treatments are proposed (see Chapters 12.1 and 12.3-12.6); there is little evidence-based medicine for any of them. An accepted medical approach is to eliminate irritants, educate, and provide sexual counseling and support. Prescribe topical lidocaine to be applied several times a day to minimize afferent input to the dorsal horn, and an oral tricyclic starting at 10 mg q.h.s. and working up gradually to 100-150 mg q.h.s. Gabapentin in doses of 1000-3600 mg, in place of or in addition to the tricyclic, may be useful. Physical therapy to the pelvic floor with biofeedback complements this regimen.93 If medical treatment fails, vestibulectomy with vaginal advancement has an 80% success rate,94 reaching 95% in some studies.95

Generalized vulvodynia

General and clinical description

Burning, aching, stinging, and rawness are some of the descriptors for generalized vulvodynia and may involve all, half, or a focal point on the vulva. Symptoms may be constant or episodic, ranging from hours to days or weeks. Dyspareunia may or may not be a feature, although intercourse may trigger the pain. Other triggers include tight clothes and undergarments, prolonged sitting, standing, or walking. Urinary symptoms of burning are frequently reported.

The etiology of vulvodynia is unknown. The pain is likened to that of neuralgia, with hyperesthesia over the cutaneous distribution of the pudendal, iliohypogastric, ilioinguinal, or genitofemoral nerves from the mons to the anus. Nerve injury, compression, or entrapment is postulated.

Diagnosis is made by ruling out vulvar pain related to a specific disorder. As with other neurogenic pain, there are often no physical findings.

Treatment with tricyclic antidepressants in doses of 20-100 mg has been successful.96 Gabapentin, effective for postherpetic neuralgia and diabetic neuropathy,97,98 is also used, although it is unstudied for vulvodynia. If musculoskeletal causes are contributing to pain, physical therapy may be helpful. Surgery to release an entrapped pudendal nerve is being done in France and has just started to be performed in the USA.


The numerous etiologies for vulvar pain as a source of female sexual dysfunction mandate a careful history and physical examination to determine the source of pain and direct its treatment. An algorithm for vulvar pain is included in Chapter 9.5 (Fig. 9.5.2).


1. Steege JF, Ling FW. Dyspareunia. A special type of chronic pelvic pain. Obstet Gynecol Clin North Am 1983; 20: 779-93.

2. Harlow BL, Stewart EG. A population-based assessment of chronic unexplained vulvar pain: have we underestimated the prevalence of vulvodynia? JAMA 2003; 58: 82-8.

3. Reed BD, Crawford S, Couper M et al. Pain at the vulvar vestibule: a web-based survey. J Lower Gen Tract Dis 2004; 8: 48-57.

4. International Society for the Study of Vulvovaginal Disease, XVII World Congress, Jointly Sponsored by the American College of Obstetricians and Gynecologists, 12-16 October 2003, Salvador, Brazil.

5. Corey L, Handsfield HH. Genital herpes and public health: addressing a global problem. JAMA 2000; 283: 791-4.

6. Margesson LJ. Infectious diseases of the vulva. In BK Fisher, LJ Margesson, eds. Genital Skin Disorders; Diagnosis and Treatment. St Louis: Mosby, 1998: 131-3.

7. Oriel JD. Infective conditions of the vulva. In CM Ridley, SM Neill, eds. The Vulva, 2nd edn. London: Blackwell Science, 1999: 103-7.

8. Ashley RL, Wald A. Genital herpes: a review of the epidemic and potential use of type-specific serology. Clin Microbiol Rev 1999; 12: 1-8.

9. Yeung-Yue KA, Brentjens HM, Lee PC et al. Herpes simplex viruses 1 and 2. Dermatol Clin 2002; 20: 249-66.

10. Barton SE, Ebel CE, Kirchner JT et al. The clinical management of recurrent genital herpes: current issues and future prospects. Herpes 2002; 9: 15-20.

11. World Health Organization Department of HIV/AIDS. Global prevalence and incidence of selected curable sexually transmitted infection. 2001.

12. Laga M, Manoka A, Kivuvu M et al. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS 1993; 7: 95-102.

13. Donders GG, Prenen H, Verbeke G et al. Impaired tolerance for glucose in women with recurrent vaginal candidiasis. Am J Obstet Gynecol 2002; 187: 989-93.

14. Fidel PL, Cutright J, Steele C. Effects of reproductive hormones on experimental vaginal candidiasis. Infect Immun 2000; 68: 651-7.

15. Sobel JD. Management of patients with recurrent vulvovaginal candidiasis. Drugs 2003; 63: 1059-66.

16. Sobel JD, Faro S, Force RW et al. Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998; 178: 203-11.

17. Schaaf VKM, Perex-Stable EJ, Borchardt K. The limited value of symptoms and signs in the diagnosis of vaginal infections. Arch Intern Med 1990; 150: 1929-33.

18. Ferris DG, Dekle C, Litaker MS. Women’s use of over-the-counter antifungal pharmaceutical products for gynecologic symptoms. J Fam Pract 1996; 42: 595-600.

19. Horowitz BJ, Giaquinta D, Ito S. Evolving pathogens in vulvovaginal candidiasis: implications for patient care. J Clin Pharmacol 1992; 32: 248-55.

20. Sobel JD, Kapernick PS, Zervos M et al. Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole. Am J Obstet Gynecol 2001; 185: 363-9.

21. Sobel JD, Chaim W, Nagappan Vetal. Therapy of vaginitis due to Candida glabrata: use of topical boric acid and flucytosine. Am J Obstet Gynecol 2003; 189: 1297-1300.

22. World Health Organization, Department of HIV/AIDS. Global prevalence and incidence of selected curable sexually transmitted infections. 2001. Available at: www.who/int/docstore/hiv/GRSTI/ 006.htm.

23. Cotch MF, Pastorek JG, Nugent RP et al. Trichomonas vaginalis associated with low birth weight and pre-term delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis 1997; 24: 353-60.

24. Wendel KA, Erbelding EJ, Gaydos CA et al. Trichomonas vaginalis polymerase chain reaction compared with standard diagnostic and therapeutic protocols for detection and treatment of vaginal trichomoniasis. Clin Infect Dis 2002; 35: 576-80.

25. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines. 2002. MMWR Morb Mortal Wkly Rep 2002; 51(RR-6): 44-5.

26. Margesson LJ. Infectious diseases of the vulva. In BK Fisher, LJ Margesson, eds. Genital Skin Disorders; Diagnosis and Treatment. St Louis: Mosby, 1998: 133-4.

27. Brown D. Herpes zoster of the vulva. Clin Obstet Gynecol 1972; 15: 1010-14.

28. Chen TM, George S, Woodruff CA et al. Clinical manifestations of varicella-zoster virus infection. Dermatol Clin 2002; 20: 267-82.

29. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med 2002; 347: 340-6.

30. Alder BS, Lewis PR. Treatment of postherpetic neuralgia: a systematic review of the literature. J Fam Pract 2002; 51: 121-8.

31. Johnson RW. Consequences and management of pain in herpes zoster. J Infect Dis 2002; 186(Suppl 1): S83-90.

32. Margesson LJ. Pediatric vulvar disorders. In M Black, M McKay. Obstetric and Gynecologic Dermatology, 2nd edn. London: Mosby, 2002: p 130.

33. Cheng SX, Chapman MS, Margesson LJ et al. Genital ulcers caused by Epstein-Barr virus. J Am Acad Dermatol 2004 (in press).

34. Sisson BA, Glick L. Genital ulceration as a presenting manifestation of infectious mononucleosis. J Pediatr Adolesc Gynecol 1998; 11: 185-7.

35. Hudson LB, Perlman SE. Necrotizing genital ulcerations in a pre- menarchal female with mononucleosis. Obstet Gynecol 1998; 92(4 pt2): 642-4.

36. Margesson LJ. Inflammatory Diseases of the Vulva. In Fisher BK, Margesson LJ, eds. Genital Skin Disorders: Diagnosis and Treatment. St. Louis: Mosby, 1998: 69-72.

37. Lynch PJ, Edwards L. Red plaques with papulosquamous features. In PJ Lynch, L Edwards, eds. Genital Dermatology. New York: Churchill Livingstone, 1994: 63-72.

38. Ridley CM, Neill SM. Non-infective cutaneous conditions of the vulva. In CM Ridley, SM Neill, eds. The Vulva, 2nd edn. London: Blackwell Science, 1999: 164-8.

39. Lewis FM, Shah M, Harrington CI. Vulval involvement in lichen planus: a study of 37 women. l 1996; 135: 89-91.

40. Lewis FM. Vulval lichen planus.  1998; 138: 569-75.

41. Rogers RS III, Eisen D. Erosive oral lichen planus with genital lesions. The vulvovaginal-gingival syndrome and the peno-genital syndrome. Dermatol Clin 2003; 21: 91-8.

42. Ramer MA, Altchek A, Deligdisch Letal. Lichen planus and the vulvovaginal-gingival syndrome. J Periodontol 2003; 74: 1385-93.

43. Lynch PJ, Edwards L. White patches and plaques. In PJ Lynch, L Edwards, eds. Genital Dermatology. Baltimore: Churchill Livingstone, 1995: 149-58.

44. Ridley CM, Neill SM. Non-infective cutaneous conditions of the vulva. In CM Ridley, SM Neill, eds. The Vulva, 2nd edn. London: Blackwell Science, 1999: 154-64.

45. Margesson LJ. Inflammatory Diseases of the Vulva. In Fisher BK, Margesson LJ, eds. Genital Skin Disorders: Diagnosis and Treatment. St Louis: Mosby, 1998: 189-93.

46. Tasker GL, Wojnarwoska F. Lichen sclerosus. Clin Exp Dermatol 2003; 28: 128-33.

47. Neill SM, Tatnall FM, Cox NH. Guidelines for the management of lichen sclerosus. sclerosus. Lancet 1999: 353: 1777-83.

49. Wakelin SH, Marren P. Lichen sclerosus in women. Clin Dermatol 1997; 15: 155-69.

50. Lynch PJ. Lichen simplex chronicus (atopic/neurodermatitis) of the anogenital region. DEdwards L. Red plaques with eczematous features. In PJ Lynch, L Edwards, eds. Genital Dermatology. New York: Churchill Livingstone, 1994: 27-34.

52. Ridley CM, Neill SM. Non-infective Cutaneous Conditions of the Vulva. In Ridley CM, Neill SM, eds. The Vulva, 2nd ed. London: Blackwell Science, 1999:151-2.

53. Ball SB, Wojnarowska F. Vulvar dermatoses: lichen sclerosus, lichen planus and vulval dermatitis/lichen simplex chronicus.

54. Virgili A, Bacilieri S, Corazza M. Evaluation of contact sensitization in vulvar lichen simplex. J Reprod Med 2003; 48: 33-6.

55. Virgili A, Bacilieri S, Corazza M. Managing vulvar lichen simplex chronicus. J Reprod Med 2001; 46: 343-6.

56. Rogers RS 3rd. Complex aphthosis. Adv Exp Med Biol 2003; 528: 311-16.

57. Rogers RS 3rd. Pseudo-Behcet’s disease. DermatolCljn2003; 21: 49-61.

58. Rogers RS 3rd. Recurrent aphthous stomatitis in the diagnosis of Behcet’s disease. Yonsei Med J 1997; 38: 370-9.

59. Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg 1997; 16: 278-83.

60. McCarthy MA, Garton RA, Jorizzo JL. Complex aphthosis and Behcet’s disease. 003; 21: 41-8.

61. Lynch PJ, Edwards L. Non-infectious primary ulcers. In PJ Lynch, L Edwards, eds. Genital Dermatology. New York: Churchill Livingstone, 1994: 213-16.

62. Margesson LJ. Contact dermatitis of the vulva. Dermatol Ther 2004; 17: 20-7.

63. Marren P, Wojnarowska F, Powell S. Allergic contact dermatoses and vulvar dermatoses. Br J Dermatol 1992; 126: 52-6.

64. Goldsmith PC, Rycroft RJ, White IR et al. Contact sensitivity in women with anogenital dermatoses. Contact Dermatitis 1997; 36: 174-5.

65. Kazaks EL, Lane AT. Diaper dermatitis. Pediatr Clin North Am 2000; 47: 909-19.

66. Lynch PJ, Edwards L. Red Plaques with Eczematous Features. In Lynch PJ, Edwards L, eds. Genital Dermatology. Edinburgh: Churchill Livingstone, 1994: 34-41.

67. Margesson LJ. Inflammatory Disorders of the Vulva. In Fisher BK, Margesson LJ, eds. Genital Skin Disorders; Diagnosis and Treatment. St. Louis: Mosby, 1998:155-7.

68. Van Seters M, van Beurden M, Burger MP et al. Preliminary results of a randomized controlled trial of imiquimod 5% cream in multifocal high grade vulvar intraepithelial neoplasia. International Society for the Study of Vulvovaginal Disease, XVII World Congress, 12-16 October, 2003, Salvador, Brazil.

69. Ridley CM, Neill SM. Non-infective cutaneous conditions of the vulva. In Ridley CM, Neill SM, eds. The Vulva. Oxford: Blackwell Science, 1999: 163.

70. Watson CPN. Post-herpetic neuralgia: clinical features and treatment. In HL Fields, ed. Pain Syndromes in Neurology. London: Butterworths, 1990: 223-38.

71. Ragozzino MW, Melton LJ III, Kurland LT et al. Population based study of herpes zoster and its sequelae. Medicine (Baltimore). 1982; 61: 310-16.

72. Loeser JD. Herpes zoster and post-herpetic neuralgia. In JJ Bonica, ed. The Management of Pain, 2nd edn. Philadelphia: Lea and Febiger, 1990; 257-64.

73. Pappagallo M, Haldey EJ. Pharmacological management of postherpetic neuralgia. CNS Drugs 2003; 17: 771-80.

74. Oaklander AL, Bowsher D, Galer B et al. Herpes zoster itch: preliminary epidemiological data. JPain 2003; 4: 338-43.

75. Watson CP, Evans RJ, Watt VR et al. Post-herpetic neuralgia: 208 cases. J Pam 1988; 35: 289-97.

77. Nurmikko, T. Clinical features in pathophysiological mechanisms in post-herpetic pain neuralgia. Neurology 1995; 45(Suppl 8): S54-5.

78. Oaklander AL, Rissmiller JG. Post-herpetic neuralgia after shingles: an under-recognized cause of chronic vulvar pain. Obstet Gynecol 2002; 99: 625-8.

79. Rowbotham M, Harden N, Bernstein SB et al. Gabapentin for the treatment of post-herpetic neuralgia: a randomized control trial. JAMA 1998; 280: 1837-42.

80. Dworkin RH, Backonja M, Rowbotham M et al. Advances in neuropathic pain. Diagnosis, mechanisms and recommendations. Arch Neurol 2003; 60: 1524-34.

81. Meana M, Binik YM, Khalife Setal. Biopsychosocial profile of women with dyspareunia. Obstet Gynecol 1997; 90: 583-7.

82. Tarr G, Selo-Ojeme DO, Onwude JL. Coexistence of vulvar vestibulitis and interstitial cystitis. Acta Obstet Gynecol Scand 2003; 82: 969-71.

83. Solomons CC, Melmed MH, Heitler SM. Calcium citrate for vulvar vestibulitis. A case report. J Reprod Med 1991; 36: 879-82.

84. Witkin SS, Gerber S, Ledger WJ. Differential characterization of women with vulvar vestibulitis syndrome. Am J Obstet Gynecol 2002; 187: 589-94.

85. Bazin S, Bouchard C, Brisson Jetal. Vulvar vestibulitis syndrome: an exploratory case-control study. Obstet Gynecol 1994; 83: 47-50.

86. Ashman RB, Ott AK. Autoimmunity as a factor in recurrent vaginal candidosis and the minor vestibular gland syndrome. J Reprod Med 1989; 34: 264-6.

87. Morin C, Bouchard C, Brisson Jetal. Human papillomaviruses and vulvar vestibulitis. Obstet Gynecol 200; 95: 683-7.

88. Foster DC, Hasday JD. Elevated tissue levels of interleukin-1 beta and tumor necrosis factor-alpha in vulvar vestibulitis. Obstet Gynecol 1997; 89: 291-6.

89. Bohm-Starke N, Hilliges M, Brodda-Jansen G et al. Psychophysical evidence of nociceptor sensitization in vulvar vestibulitis syndrome. JpOn 2001; 94: 177-83.

90. Gerber S, Bongiouvanni AM, Ledger WJ et al. Defective regulation of the proinflammatory immune response in women with vulvar vestibulitis syndrome. Am J Obstet Gynecol 2002; 186: 696-700.

91. Friedrich EG. Vulvar vestibulitis syndrome. J Reprod Med 1987; 32: 110-14.

92. Bergeron S, Binik YM, Khalife Setal. Vulvar vestibulitis syndrome: reliability of diagnosis and evaluation of current diagnostic criteria. ObstetGynecol 2001; 98: 45-51.

93. Glazer HI, Rodke G, Swencionis  C et al. Treatment of vulvar vestibulitis syndrome with electromyographic biofeedback of pelvic floor musculature. J Reprod Med 1995; 40: 283-90.

94. Bergeron S, Binik YM, Khalife Setal. A randomized comparison of group cognitive-behavioral therapy, surface electromyographic biofeedback, and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis. JPain 2001; 91: 297-306.

95. Marinoff SC, Turner ML, Hirsch RP et al. Intralesional alpha- interferon: cost effective therapy for vulvar vestibulitis syndrome. J Reprod Med 1993; 38: 19-24.

96. McKay M. Dysesthetic (“essential”) vulvodynia. Treatment with amitriptyline. J Reprod Med 1993; 38: 9-13.

97. Backonja M, Beydoun A, Edwards KR et al., for the Gabapentin Neuropathy Study Group. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus, a randomized controlled trial. JAMA 1998; 280: 1831-6.

98. Rowbotham M, Harden N, Stacey B et al., for the Gabapentin Neuralgia Study Group. Gabapentin for the treatment of postherpetic neuralgia, a randomized controlled trial. JAMA 1998; 280: 1837-42.