Erosive vulvovaginal lichen planus affects adults only, and women are far more often affected by the erosive form, particularly in the United States where circumcision is regularly performed on most newborn boys. Fewer than 25% of women with genital lichen planus have concurrent cutaneous involvement. Patients often report pruritus, but no pleasure with scratching, although the predominant complaint is that of burning, irritation, rawness, dysuria, dyspareunia, and postcoital bleeding. Many patients with erosive genital lichen planus also report mouth pain, especially with hard food such as chips, spicy foods, and acidic foods.

Although lichen planus manifests with many different morphologic appearances, classic lesions on keratinized skin are pruritic, violaceous, flat-topped papules (see Chapter 3). However, on mucous membranes, the most common morphologies are white lacy papules and plaques (see Chapter 11) or erosions. The white and eroded lesions can present separately or together. In 1982, Pelisse and associates described the vulvovaginalgingival syndrome, introducing erosive lichen planus as a separate subgroup in women. Characteristically, these patients suffer erosions of the vulva, vagina, and oral mucosa at some stage of the disease, although not necessarily initially. Involvement of the modified mucous membranes of the vulva is usual, with bright red, thin epithelium and erosions most marked in the vestibule. These can be nonspecific, but often surrounding white epithelium and reticulate white lacy plaques reveal the diagnosis of lichen planus (Figs. 9-1, 9-2, 9-3, 9-4 and 9-5). With chronic erosive lichen planus, scarring occurs (Fig. 9-6). Labial resorption and scarring of the clitoral hood over the clitoris are common. Narrowing of the introitus is also a frequent complication.

Vaginal erosions are usual with erosive vulvar lichen planus (Fig. 9-7). Even when vulvar lichen planus is papular rather than erosive, accompanying inflammatory vaginitis produced by lichen planus is common (see Chapter 15). Erosive vaginal lichen planus is tender and chronic and produces purulent vaginal secretions that incite an irritant contact dermatitis in the vestibule. Vaginal adhesions occur with severe disease, sometimes producing obliteration of the vaginal space that make sexual intercourse or the introduction of a speculum impossible.

Gingival lesions may be localized or generalized, primarily manifested by tender erosions and desquamative gingivitis, sometimes with surrounding solid or reticulate white papules (Fig. 9-8). Often, linear reticulate papules or erosions occur on the buccal mucosa (Fig. 9-9). Esophageal lichen planus is increasingly recognized and is more common than the literature suggests. Strictures
producing dysphagia and weight loss are suggestive of this involvement, and squamous cell carcinoma of the esophagus is a serious complication (1).

Penile lichen planus is more commonly associated with lichen planus at other cutaneous sites than is vulvovaginal
lichen planus. Lesions are less often eroded, but when erosions occur, they are very painful (Figs. 9-10 and 9-11). These erosions may be associated with oral lesions and run a similar prolonged clinical course to that seen in women (2). Men with erosive penile lichen planus also experience scarring, with phimosis if uncircumcised, or obliteration of the sharp distinction of the glans from the
shaft in the circumcised penis. Perianal lesions sometimes occur in both genders (Fig. 9-12).

There are rare reports of squamous cell carcinoma occurring in both vulvar and penile lichen planus. Indurated erosions and ulcers should be biopsied, as should chronic hyperkeratotic areas.

There have been reports of lichen planus occurring more often in patients with hepatitis C, and reports discounting this association. A recent meta-analysis reports that this association is real, at least in some geographic locations (3).

The diagnosis of lichen planus can be made with confidence when erosions are accompanied by white, lacy, reticulate, or fernlike papules of the genitalia or mouth. Otherwise, a biopsy is required, although most often the histology is returned as “lichenoid dermatitis” consistent with but not diagnostic of lichen planus. The biopsy should be taken from the edge rather than the center of an erosion, and it should be submitted for routine histology. If the biopsy is very nonspecific or is suggestive of an autoimmune blistering disease such as cicatricial pemphigoid or pemphigus vulgaris, an additional biopsy submitted for direct immunofluorescence will be necessary. This biopsy should be obtained from normal, perilesional skin and stored in transport media rather than formalin.

Histologic features of erosive lichen planus include a dense, lymphocytic, dermal bandlike infiltrate extending to and damaging the basal layer. A prominent granular cell layer, hyperkeratosis, and acanthosis are common, but erosive mucous membrane lichen planus often exhibits epithelial thinning and flattening. A biopsy of eroded skin that does not include epithelium cannot demonstrate a diagnosis of lichen planus, so biopsy sampling should include the epithelialized edge of an erosion. Colloid and Civatte bodies are frequently seen in the lower epidermis and upper dermis, and a direct immunofluorescent biopsy makes these more easily visualized.

Most chronic erosive skin diseases are in the differential diagnosis of erosive genital lichen planus. Pemphigus vulgaris and cicatricial pemphigoid are nearly indistinguishable, but less common and usually more easily diagnosed by routine and direct immunofluorescent biopsy. Often, surrounding white epithelium suggests the diagnosis of erosive lichen planus, but any chronic erosion can induce surrounding nonspecific white epithelium. Sometimes, this white epithelium can resemble lichen sclerosus, but lichen sclerosus never affects the vagina, and it shows a characteristic crinkled or occasionally waxy texture unlike that of lichen planus. Toxic epidermal necrolysis, severe erosive candidiasis, and an irritant contact dermatitis to an agent such as podophyllum resin can mimic erosive lichen planus, but these are acute rather than chronic in onset. Like erosive lichen planus, plasma cell mucositis also exhibits red, moist, glistening papules, and plaques that may appear erosive. The histology differentiates lichen planus from plasma cell vulvitis or balanitis and from the erosive genital lesions of graft versus host disease that may also be associated with lichenoid skin lesions.

Lichen planus is an inflammatory condition of unknown etiology. However, evidence suggests this disorder may be an autoimmune disease of cellular immunity. Injury of the basement membrane by cytotoxic T cells is
central, and recent investigations report amplification of this injury by interferon alpha derived from plasmacytoid dendritic cells (4). Other autoimmune diseases cluster with lichen planus, including lichen sclerosus (5).

The management of erosive lichen planus often is difficult. Mild disease is often adequately controlled by supportive measures and topical corticosteroids, whereas more severe disease requires the systemic use of systemic antimetabolites and immunosuppressive agents with variable success. Circumcision is sometimes curative in men (6).

Topical emollients such as petrolatum are soothing, as are measures such as air-drying rather than towel-drying. Because vulvovaginal lichen planus occurs primarily in the postmenopausal age group, topical or systemic estrogen replacement can be crucial, avoiding an additional and easily corrected cause for mucosal thinning.

First-line specific therapy for lichen planus is corticosteroid therapy. Potent topical steroid ointments (e.g., clobetasol propionate 0.05%) applied to vulvar or penile lesions twice daily can be beneficial. Creams, gels, lotions, and solutions are to be avoided because of the irritation induced by the alcohols regularly contained in these vehicles. This medication can also be inserted intravaginally at night, as can 25 mg hydrocortisone acetate rectal suppositories or hydrocortisone foam.

Systemic corticosteroids (prednisone 40 to 60 mg/day) effect significant and rapid improvement in most patients, but the condition recurs when the medication is stopped. The benefit is delayed in onset for all other treatments, and other therapies improve lichen planus less regularly. Methotrexate 25 mg weekly sometimes is beneficial for lichen planus (7). There are reports that oral retinoids such as isotretinoin 40 to 80 mg/day and acitretin at about 25 mg/day have been helpful, but side effects including teratogenicity and altered liver function require careful monitoring, and more evidence is needed from larger clinical trials as to their effectiveness. In addition, the long half-life of some retinoids is problematic. Other systemic treatments tried include oral griseofulvin at 500 mg twice daily, dapsone 100 to 150 mg daily, azathioprine, cyclophosphamide, mycophenylate mofetil, and hydroxychloroquine 200 mg twice daily, with anecdotal benefit in some patients; clinician familiarity with these medications for appropriate monitoring is important. Topical cyclosporine (using the oral liquid or solution intended for intravenous administration) four times a day has been useful for occasional patients, but the expense, local irritation, and minimal benefit render it impractical for most (8). Thalidomide at 100 to 150 mg/day is a theoretical potential therapy (9), as are topical tacrolimus (10) and pimecrolimus (11). More recently, topical rapamycin has been suggested as beneficial for refractory oral erosive lichen planus (12). Extracorporeal photochemotherapy has been reported beneficial in a series of patients with refractory oral erosive lichen planus, an expensive therapy not available to most clinicians (13). No one therapy is ideal, and few produce consistent improvement without significant risks or side effects.

Lastly, surgery is occasionally needed to separate vaginal adhesions, reverse tightening of the introitus, or to uncover a buried clitoris. Skin disease should be controlled as well as possible before surgery is contemplated, and great care has to be taken postoperatively to prevent rapid scar reformation. Use of topical steroids and dilators is advisable.

Erosive anogenital lichen planus is chronic and painful, and there are no standard treatment measures that help all patients. Nor are there any controlled trials that evaluate therapy for anogenital lichen planus. However, experience suggests that there are various therapies that help some patients. Occasionally, erosive anogenital lichen planus remits, but this is the exception. Also, because of the risk of squamous cell carcinoma, patients should be checked regularly throughout the course of the disease.

Plasma cell vulvitis and balanitis present as a glistening, red, usually solitary plaque on the glans penis or vulva (Figs. 9-13 and 9-14). This may be asymptomatic or may present with mild pruritus. Erosive and vegetative types may occur, which are more painful. Lesions may
persist for years, but they usually resolve slowly leaving a “rusty stain” resulting from microhemorrhage and hemosiderin deposition. The condition may recur.

Plasma cell vulvitis and balanitis are diagnosed by the morphology of characteristic skin lesions, and it is confirmed on biopsy. Histology shows a thinned epidermis, sometimes with upper layers absent or detached from the dermis. Flattened keratinocytes separated by intercellular edema are distinctive. Red blood cells may be seen in the upper dermis and epidermis, and hemosiderin and vascular proliferation are common in the dermis. A dermal bandlike dense infiltrate with a predominance of plasma cells is characteristic.

Other diseases that can be confused with plasma cell vulvitis and balanitis include erosive lichen planus, intraepithelial neoplasia (also called Bowen disease, erythroplasia of Queyrat), and sometimes, Paget disease. Erosive candidiasis also can resemble Zoon vulvitis or balanitis.

The pathogenesis of plasma cell mucositis is unknown. Some believe that this may be related to lichen planus, and others suspect it is a nonspecific reaction pattern to an inflammatory process.

Most common in younger individuals, herpes simplex virus infection is especially likely in those who have higher risks of contagion due to many lifetime sexual partners. HSV produces both primary and recurrent infections. Primary infection with HSV is often subclinical and unrecognized, but the classic primary infection by HSV is much more severe than recurrent episodes. Primary genital HSV infection follows exposure by 2 to 7 days and often exhibits associated fever, malaise, headache, and other constitutional symptoms. Regional lymphadenopathy is usual; pain and edema may cause urinary retention. The lesions initially occur as small (1- to 3-mm), scattered, and grouped vesicles occurring typically on the glans or shaft of the penis or the mucous membrane and modified mucous membrane portion of the vulva, sometimes extending to keratinized skin (Figs. 9-19, 9-20 and 9-21). Because the vesicles are fragile and easily break, well-demarcated, discrete, round, and arcuate erosions (which indicate coalescing of the round erosions) often are seen rather than intact vesicles, especially on modified mucous membrane skin (Figs. 9-22, 9-23 and 9-24). Healing may be complicated by secondary infection and irritation from overwashing or topical agents used empirically by an anxious patient.

After a primary infection, HSV remains latent in neuronal cells located in ganglia. Subsequently, the virus intermittently reactivates, thus producing recurrent disease that is usually milder and shorter in duration. Recurrent genital HSV infections are less painful, more localized, and less often associated with fever, arthralgias, and headache than primary disease. Many patients experience
a prodrome of tingling, burning, or dysesthesias before the onset of skin lesions. Recurrent HSV is most often located on the glans and shaft of the penis and the mucous membranes and modified mucous membrane portion of the vulva, but can occur on any epithelial surface, including the scrotum, perianal skin, and hair-bearing labia majora. Recurrent episodes are characterized by grouped vesicles that quickly develop into well-demarcated, round, and arcuate erosions. On dry, keratinized skin such as the shaft of the penis or the hair-bearing labia majora, round crusts may be the predominant lesion. Linear fissures can appear as a manifestation of HSV infection, occurring most often in skin folds, such as the interlabial sulci of the vulva or within normal skin wrinkling of the penile shaft.

The primary episode of HSV infection for many patients is subclinical, so these people do not experience a classic primary episode of HSV infection and are thus unaware of their infection. Thus, their first clinical episode of infection exhibits the localized grouping of vesicles and
erosions and milder clinical course of recurrent HSV infection. Because the appearance of this nonprimary but first clinical episode is delayed, the time and circumstances of transmission cannot be determined; on occasion, this delay is years long.

HSV infections often are associated with marked morbidity in immunosuppressed patients (see Chapter 16). Patients with altered cellular immunity, as occurs in those with HIV disease and patients receiving immunosuppressive agents, are at increased risk of ulcerative and chronic HSV infection (Fig. 9-25).

Although the diagnosis usually can be made on the appearance of skin lesions and history, laboratory confirmation of a genital HSV infection is desirable because of the psychologic impact of this disease on the patient and his or her partner. A viral culture from a swab of the base of a fresh erosion is the most common means of detecting HSV. However, false-negative results are a common occurrence in many laboratories, especially when delivery of the sample to the laboratory is delayed. Therefore, a negative culture should not convince a suspicious clinician to eliminate the diagnosis. Recently, the extremely sensitive polymerase chain reaction technique for detecting HSV has become widely available and reasonably priced, so this is now a test of choice (21). Although more uncomfortable, a shave skin biopsy from the edge of an erosion or of an intact vesicle is another very sensitive test to confirm the presence of a herpes virus infection, but a biopsy does not differentiate HSV from VZV. The Tzanck’s preparation, although very quick, is less reliable, even in experienced hands. Direct immunofluorescent antibodies are available for HSV1 and 2 for more rapid diagnosis, although an adequate sample is of utmost importance. Scraping the base of the ulcer with a number 15 blade usually suffices for an adequate cell sample. Serology is not an adequate means of diagnosing an episode of HSV. Positive IgG for HSV varies very widely according to the country, occurring in up to 80% of adults; this denotes exposure, but not active or communicable disease (22). Negative serology indicates no past infection, but does not rule out a primary episode, since about 6 weeks is required for conversion.

The histologic appearance of HSV includes an intraepidermal vesicular dermatitis formed by acantholysis. Individual keratinocytes show intracellular edema (ballooning) and reticular degeneration (intracellular edema causing cell walls to burst). Eosinophilic intranuclear inclusion bodies may be present. Multinucleated keratinocytes are pathognomic for herpes virus infections but do not distinguish between HSV and varicella-zoster virus (VZV) infections.

HSV must be differentiated from several other vesicular and pustular diseases. Occasionally, the differentiation of genital HSV infection from VZV infection can be difficult, because both exhibit grouped vesicles or erosions. However, genital VZV infection usually occurs in the older patient and covers a dermatomal pattern, also affecting the medial thigh or buttock unilaterally. VZV infection occurs only once in the immunocompetent patient, rather than recurrently, as is usual with HSV infection. Another likely disease to confuse with genital HSV infection is candidiasis of the modified mucous membranes of the vulva or the uncircumcised glans penis, in which yeast can cause coalescing erosions when superficial pustules rupture. A fungal smear is positive in that case. Folliculitis, both irritant and staphylococcal, produces discrete red papules and pustules that can mimic HSV. Finally, blistering erythema multiforme both mimics and sometimes follows HSV infection. The most common cause of recurrent erythema multiforme is recurrent HSV infection in a patient with an enhanced immunologic response to this virus. These patients usually exhibit both intraoral and genital erosions that are less well demarcated, whereas HSV does not occur inside the mouth, except for the initial primary outbreak. In addition, the occurrence of red, nonscaling, flat-topped papules on the palms, soles, and sometimes other keratinized surfaces is common.

Herpes simplex virus (HSV) types 1 and 2 are doublestranded DNA viruses (Herpesvirus hominis) capable of producing vesicular and erosive mucocutaneous disease. Oral mucocutaneous and ocular disease is produced by HSV 1 in most cases, whereas genital HSV infection is caused by HSV 2 in the majority of affected patients. The proportion of HSV 1 occurring on the genital skin is increasing, presumably due to the increase in oral-genital sexual activity.

The management of HSV infection begins with the sensitive and nonjudgmental education of the patient. The patient should be counseled regarding the infectious nature of the disease, its recurrent nature, and the importance of avoidance of sexual intercourse when open lesions are present. Circumcision and condoms have been shown to confer modest protection from infection (23,24). Patients should be aware that intermittent shedding of the virus occurs when there is no evidence of active HSV infection, and the infection can be transmitted even in the absence of blisters and erosions. In fact, most HSV infection is contracted during asymptomatic episodes. This shedding has also been documented in patients receiving long-term suppressive antiviral medication. Therefore, the use of a condom, even when there are no obvious lesions, is wise. The possibility of transmission of HSV to a newborn during delivery should be discussed to ensure the protection of future infants from maternal infection, although most neonatal HSV infections occur due to maternal primary infection.

Both primary and recurrent primary HSV infections are shortened by prompt treatment with specific oral antiviral agents, although some recurrent episodes are so mild that therapy is unwarranted. Three current choices for the treatment of recurrent HSV are as follows: 5 days of acyclovir 200 mg five times a day (or, for primary HSV infection, for 10 days), famciclovir 125 mg twice daily, and valacyclovir 500 mg twice daily (1 g twice daily for 10 days for primary HSV infection). These therapies exhibit equivalent efficacy, with choices made on the basis of cost and convenience of dosing. Side effects are minimal with each. Topical acyclovir exerts only minimal benefit. More recently, topical penciclovir has become available to shorten the course of HSV infection, but the benefit over placebo is minimal.

Intravenous acyclovir is occasionally needed if disease is severe, especially if the patient is immunosuppressed or if gastrointestinal absorption is a major problem, as can occur in the HIV-positive patient. Resistance of HSV to currently available oral medications occurs only occasionally and always in immunosuppressed patients. Foscarnet is an alternative treatment, although it is available only for intravenous use. Several other agents have been reported as beneficial in acyclovir-resistant HSV, including intravenous and topical cidofovir, topical trifluorothymidine, topical interferon-α in dimethyl sulfoxide, and imiquimod (25).

For patients experiencing frequent or severe episodes of HSV infection, chronic prophylactic acyclovir at a dose of 400 mg twice daily, famciclovir 250 mg twice daily, or valacyclovir 500 to 1000 mg/day is a safe, practical, and effective means of preventing most recurrences. Suppressive oral antiviral therapy also decreases asymptomatic shedding and, therefore, probably infectivity, but asymptomatic shedding of virus is not eliminated (26). Transmission of HSV infection still occurs in patients taking these medications and experiencing no clinical outbreaks.

Crucial to the management of anogenital HSV infection is counseling and psychological support. These patients exhibit marked anxiety, depression, fear, and selfesteem issues (27).

Some patients erroneously believe that HSV infection can be followed by postherpetic neuralgia. Fortunately,
that is not a sequel to this infection; this only follows herpes zoster infection.

Herpes zoster occurs primarily in patients with immune deficiency by virtue of age, disease, or medications, but occasionally occurs in young and healthy individuals. The prevalence of this miserable condition should decrease as more older people receive the recently available vaccine.

Many patients experience a localized prodrome of pain, itching, burning, or aching, followed in one or a few days by pink, nonscaling plaques in a unilateral dermatomal distribution (Figs. 9-26 and 9-27) in the symptomatic area. Grouped vesicles overlying these red plaques quickly follow, then coalesce into larger blisters. Often, the blisters become purple or gray due to hemorrhage into the blister. Over the next 3 weeks, the blisters crust and heal. Blisters occurring on mucous membranes and modified mucous membranes of the genitalia are quickly unroofed due to friction on this moist and very thin skin, so that erosions usually predominate. Likewise, the friction from skin folds and clothing often tears blister roofs even on the more keratinized genital skin. Herpes zoster can become ulcerative, chronic, or hyperkeratotic in immunosuppressed patients (see Chapter 16).

Sometimes, the eruption is accompanied by mild headache, malaise, and a low-grade fever. However, the primary complication of herpes zoster infection is the development of postherpetic neuralgia, in which chronic pain persists after the eruption resolves. This is more likely in individuals over 60 years of age and in immunosuppressed people. Some clinicians theorize that this may be responsible for some genital pain syndromes such as vulvodynia and scrotodynia, but preceding VZV infection affecting the genitalia is almost never identified in patients with genital pain syndromes. Unlike HSV, VZV does not recur in immunocompetent patients.

The definitive diagnosis of herpes zoster is usually made on the basis of the presentation and morphology. When necessary, this can be confirmed by a positive culture or the identification of viral DNA with the PCR technique. The virus is rather fastidious, so cultures are sometimes falsely negative, but the PCR technique is very sensitive and now easily available. Tzanck’s preparation from epithelial cells scraped from the base of a blister or erosion shows giant cells when examined microscopically, but the validity of this test is extremely dependent on the examiner, and the results are subjective. A biopsy is extremely sensitive but does not differentiate between HSV infection and herpes zoster, a distinction that can usually be made on clinical grounds. The histologic appearance of herpes zoster infection is identical to that of HSV infection. Keratinocytes swell and burst, and some epithelial cells form giant cells. Occasionally, leukocytoclastic vasculitis underlies these epithelial changes, but this does not indicate a primary or possibly systemic problem of vasculitis.

The differentiation of genital herpes zoster infection from HSV infection may be difficult. HSV is a recurrent disease, whereas herpes zoster is a one-time event, except in significantly immunosuppressed patients. Herpes zoster is unilateral, but vesicles may erode early in both diseases. Bullous impetigo and bullous pemphigoid can sometimes mimic herpes zoster, but these are usually bilateral and are not particularly painful. Bullous pemphigoid generally exhibits distant lesions that exclude the diagnosis of herpes zoster, and impetigo can be differentiated by culture.

Herpes zoster infection is a blistering disease that results from reactivation of VZV that has been latent in nerve ganglia since a remote episode of varicella. This condition occurs most often in older individuals whose immune system is less efficient or in immunocompromised patients.

For most patients with herpes zoster, pain control is the most important aspect of care. Narcotic pain analgesia is usually needed for the first few weeks. The early diagnosis and treatment (within 72, but especially 48 hours) with oral antiviral therapy somewhat reduces the duration of an acute infection. This improvement is not striking, so therapy is optional in younger, healthy patients. However, immunosuppressed or very elderly people should be treated. Some studies have shown an arguably significant reduction of postherpetic neuralgia in patients treated early.

Choices include acyclovir 800 mg five times a day, famciclovir 500 mg three times daily, and valacyclovir 1 g every 8 hours. The advantage of the more expensive valacyclovir and famciclovir is the less frequent dosing schedule.

Those patients who experience postherpetic neuralgia deserve medication for neuropathic pain, including amitriptyline, gabapentin, pregabalin, venlafaxine, or duloxetine (see Chapter 5). Sometimes, referral to a pain clinic is necessary.

Otherwise, the best current management is prevention. A vaccine for the prevention of herpes zoster is now available, approved by the Food and Drug Administration for people over 60 years of age.