Learning Objectives:After participating in this continuing professional development activity, the provider should be better able to:

1. Differentiate the various types of common vulvar ulcers in girls and women.

2. Explain recommended therapies for the conditions causing common vulvar ulcers.

3. Discuss the emotional effects that vulvar ulcers can have on patients.

This article is the first of 2 parts.

Vulvar ulcers are frequently seen not only by gynecologists but also by pediatricians, family practitioners, and emergency department physicians. They present in girls and women of all ages as painful intact or unroofed blisters, often of abrupt onset. They can lead to such severe discomfort as to make urination impossible. Although the most common cause of such ulcers is herpes simplex virus (HSV) types I and II, other causes are also not infrequent and should be part of the differential diagnosis. The first part of this review discusses the diagnosis and management of the most commonly seen causes of vulvar ulcers.

Pathophysiology of Ulcerative Vulvar Lesions

Ulcerative vulvar lesions occur after vesicles or bullae on the vulva have been unroofed. The original lesions are filled with clear or yellowish serous fluid that collects between layers of vulvar epidermal cells or between the epidermis and the dermis. These lesions are categorized by size. Vesicles are less than 1 cm (Figure 1A), whereas bullae are more than 1 cm (Figure 1B).

Figure 1. (

The degree of tenseness of the covering membrane of vesicles and bullae is due to the thickness of the layer of epithelium that becomes separated from the layer underlying it and is often a diagnostic clue. It is important to distinguish vesicles from pustules, which are also frequently seen on the vulva. Vesicles are filled with watery, serous fluid whereas pustules contain sebaceous or purulent discharge.

Approach to the Patient With Painful Vulvar Ulcers

The experienced clinician, hearing that a patient reports sudden onset of painful vulvar lesions, will often presume that the patient has a herpes simplex I or II infection. Although this supposition may be correct, it will not always be, for there are a large variety of conditions-infectious, allergic, immunologic, traumatic, drug-induced-that can cause such lesions. Thus, the clinician is well advised to keep an open mind and evaluate the lesions with which the patient presents thoroughly and systematically.

Many patients who present with vulvar lesions are already concerned about the possibility of having a herpetic infection-and the pain, recurrences, relationship issues, and stigma these involve. Thus, clinicians must be sensitive to the potential emotional trauma these patients may be experiencing.

The ideal clinical approach to patients whose presenting problem is painful vulvar lesions is the same as the general approach to any medical symptom: comprehensive history and physical examination. The history should include when the lesions first appeared, if they have evolved, and whether the onset directly followed a specific event such as trauma, a new sexual contact, the start of a new medication, or vulvar exposure to substances such as new clothes, hygiene agents, soaps, detergents, toilet paper, or sanitary products. Other symptoms should be explored such as pain, fever, rash, dysuria, lymph node swelling, arthritis, or oral lesions. It is helpful to learn whether the patient's sexual partner has had skin or genital lesions. Other important questions should address any history of such lesions, associated medical conditions known to cause vulvar ulcers such as Crohn's disease or psoriasis, or any history of dermatologic conditions in which blisters, vesicles, or bullae are seen.

Physical Examination

There are a number of key findings on physical examination that are critical to accurate diagnosis. First, one must assess whether the lesions have the classic appearance of relatively common conditions such as herpes simplex, eczema, or psoriasis. Other important findings include whether the lesions are isolated or spread over the entire vulva and whether there are one or more clusters of small (2-5 mm) vesicles or shallow ulcers as opposed to lesions larger than 5 mm. Important associated findings that should be noted include the presence of a background rash, swollen or draining lymph nodes, abnormal vaginal or rectal discharge, or tears and lacerations suggesting vulvar trauma or excoriation from scratching.

Diagnostic Testing

Although a presumptive diagnosis is often made based on history and physical examination-such as a classic history and appearance of herpes simplex or contact dermatitis-diagnostic confirmation should still be sought. Patients will want to know for certain what is causing their lesions. Such confirmation will also direct therapy and patient counseling.

Testing should be guided by history and clinical presentation. For example, a young woman presenting with a cluster of small, extremely painful vulvar ulcers after a recent new sexual contact probably needs no more than testing for HSV. On the other hand, a woman presenting with vulvar ulcers and suppurating vulvar, vaginal, or anal lesions needs testing for multiple conditions, including syphilis, chancroid, granuloma inguinale, lymphogranuloma venereum, and Crohn's disease. When there is a history of recent exposure to plants or chemicals causing pruritis, erythema, and swelling, sophisticated testing is usually not necessary. But when the presentation is unusual and lesions persist despite treatment, skin biopsies should be performed to rule out chronic skin conditions such as lichen sclerosis or vulvar neoplasia.

Immediate Therapy Before Diagnosis

If a patient's vulvar pain and swelling are severe, it may be necessary to initiate treatment before a causative mechanism is firmly established. Immediate comfort measures can include warm soaks with or without additives such as baking powder, Burow's solution, or oatmeal bath, and analgesic creams, sprays, or ointments. If the patient is having difficulty urinating, warm compresses to the vulva or lidocaine gel to the urethra may be helpful. In extreme cases, catheterization may be necessary. Oral analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) are often helpful, and even stronger oral medications including oxycodone, codeine, or meperidine may be considered in cases of debilitating pain. Topical corticosteroid creams or ointments can provide limited relief; systemic therapy is sometimes initiated in very severe cases. If a presumptive diagnosis can be made based on the history and examination, specific therapies should be initiated. These could include acyclovir, famciclovir, or valacyclovir for presumed herpes, or clobetasol or other potent corticosteroid creams and ointments for contact dermatitis.

Specific Causes of Vulvar Ulcers

Herpes Simplex I and II

There are 2 types of HSV, designated type I and type II. The majority of adults have antibodies against HSV: 70% for type I and 20% to 50% to type II.3 Traditionally, HSV I has been associated with oral lesions ("cold sores") and HSV II with genital lesions. However, likely due to the increasing diversity of sexual practices over the last 40 years, this distinction has become blurred. Nevertheless, determining which viral type is present in a specific case is important as it has prognostic significance. Recurrences with HSV I-50%-are less frequent than with HSV II: 80%.4 Moreover, those who have evidence of infection with HSV II are unlikely to become infected with HSV I exposure, but the converse is not the case: previous HSV I infection does not protect against acquiring HSV II.5

Infection with HSV is lifelong. When inactive, the virus lies dormant in the sensory ganglia of the spinal cord. What causes reactivations is unknown but often seems to be linked to physical or emotional stress. The degree of asymptomatic viral shedding is approximately 7% for HSV I and 27% for HSV II at the end of 1 year.6 Herpes simplex type II is frequently seen as a coinfection in individuals with HIV.

Other than the pain of the lesions and the risk of infecting partners, the vast majority of adults suffer few adverse consequences from HSV infections. Some individuals, however, do have more extensive involvement, which can include aseptic meningitis, acute urinary retention with loss of sacral sensation, proctitis, chorioretinitis, and hepatitis.

Herpes infection poses significant risk during pregnancy and delivery. Primary herpes infections during pregnancy can result in spontaneous abortion, intrauterine growth restriction, preterm labor, and congenital and neonatal herpes infections.7 Pregnant patients with a primary herpes infection or recurrent lesions at the time of labor are at risk of fetal infection either by viral ascent through the birth canal or via direct fetal contact with maternal lesions. Women with a history of herpes recurrences are often treated with prophylactic antiviral medication from 36 weeks' gestation until delivery. Neonatal complications from herpes infection may be life threatening, and can include skin, mouth, eye, and central nervous system infections and disseminated disease. Cesarean delivery is considered in women approaching delivery with evidence of current herpes simplex lesions.

Clinical Presentation

Patients with vulvar herpes simplex infections generally present with the acute onset of painful vulvar lesions, often in small clusters, anywhere on the mons, labia, perineum, or perianal areas. These are often accompanied by itching, burning, and tingling. Manifestation of infection will often start with the eruption of small (<5 mm) vesicles on some area of the vulva, which then rupture, producing a clear, yellowish fluid and leaving painful small ulcerations (Figure 2). These ulcerations may coalesce into larger denuded skin patches. The lesions often overlie an erythematous rash and are accompanied by tender inguinal lymphadenopathy.

Figure 2. Genital herpes infection.

The pain of the vulvar lesions can be excruciating and can cause severe dysuria secondary to contact of urine with the lesions. If this is a patient's first episode of herpetic infection, she might also have viremia with a febrile illness lasting for 3 to 5 days marked by fever, chills, and generalized malaise. Symptoms and lesions appear 2 to 12 days after exposure to the infectious source, which is usually but not exclusively some form of sexual contact. Herpes simplex viral spread can also be due to autoinoculation if an individual who has oral herpetic sores touches them and then touches her vulva. Recurrences of the lesions are common, but symptoms are typically less severe than with the primary episode.

Patients who present with painful vulvar lesions are often extremely anxious and upset. Not only are they in significant pain, but they are also fearful about the implications of a herpetic infection. They are often concerned about the prospect of persistent recurrences and are frequently embarrassed and/or ashamed that they have gotten this infection. It is common for these patients to be angry at their partners for infecting them and frightened about what this infection might mean for future relationships and pregnancy. Clinicians must be both aware of these concerns and empathetic in dealing with these significant emotional issues.

Diagnosis

Diagnosis can usually be made by history and the visual appearance of the lesions. The differential diagnosis includes herpes zoster, contact dermatitis (eg, poison ivy), dermatologic drug reactions, and a few rarer conditions. Because of these potential other causes, the diagnosis should be confirmed by more objective measures whenever possible.

In addition to the history and physical findings described previously, polymerase chain reaction (PCR)/DNA testing is the current standard to establish the diagnosis.9 These tests have a high sensitivity and specificity. Culture of the lesion is no longer the first option, and the Tzanck prep, which is still sometimes mentioned in textbooks, is obsolete. The older the lesions are, the less likely it is that HSV DNA will still be present, making for a high rate of false-negative testing in patients who present later in their HSV course. Unlike other infections, serologic testing is generally not helpful in herpes simplex diagnosis and treatment. Herpes simplex immunoglobulin M (IgM) is not reliable as a test for recent infection, and positive herpes IgG titers only indicate that at some time in the past there has been exposure to the HSV, which, as mentioned, is present in the majority of adult patients.

Because HSV is generally acquired via sexual contact, it is not surprising that other venereal diseases would be encountered simultaneously. Therefore, best practice is to perform additional laboratory testing for gonorrhea, chlamydia, syphilis, and HIV in patients who present with initial HSV infections.

Treatment

Although there is as yet no cure for HSV infections, there are specific treatments that can either shorten the time course of attacks or decrease the frequency of recurrences.

In cases of primary HSV infection, antiviral therapy should be started as soon as possible after the appearance of lesions. This will increase their rate of healing, decrease the length of time the lesions are shedding virus, and diminish pain. There are 3 commonly used antiviral treatment regimens for herpes simplex types I and II:

1. Acyclovir: 400 mg orally 3 times/day for 7 to 10 days; or

2. Famciclovir: 250 mg orally 3 times/day for 7 to 10 days; or

3. Valacyclovir: 1000 mg orally 2 times/day for 7 to 10 days.9

All of these medications are similar in terms of the efficacy of decreasing discomfort, resolution of lesions, and decrease in viral shedding. The choice of which to use should be based on availability, convenience of dosage, and cost. Generic oral acyclovir is often the least expensive, but its frequency of dosing is off-putting to many patients. Acyclovir cream and ointment are the only topical forms of medication for HSV, but although they may be soothing, they do not shorten the duration of the lesions. IV antiviral medication is only employed when there is severe illness such as with infants or for the immunocompromised. Symptomatic treatment with comfort measures as described previously is typically initiated along with medication.

Prophylaxis

For patients who have frequent recurrences of HSV lesions, prophylactic daily administration of an antiviral medication has been shown to decrease the frequency of outbreaks. Recommended dosages for prophylactic treatment are:

* Acyclovir: 400 mg twice daily; or

* Famciclovir: 250 mg twice daily; or

* Valacyclovir: 500 mg once daily or 1000 mg once daily.9

Such therapy not only reduces the frequency of herpetic episodes but also decreases-though does not entirely eliminate-the risk of infecting sexual partners. Patients taking antiviral medications prophylactically on a continuous basis should have liver function testing at least yearly to rule out rare hepatic dysfunction.

Direct Skin Trauma-Lichen Simplex

Abrasion or other excoriation of vulvar skin, chronic moisture, or continuous pressure can cause an inflammatory response resulting in rash, epithelial denudation, and ulceration. Pruritis from such lesions may lead to continuous scratching and ultimately lichenification of the vulvar skin, called lichen simplex. This diagnosis is usually made by history and observation. Skin biopsy may sometimes be necessary to rule out lichen sclerosis, vulvar dysplasia, or carcinoma. Treatment consists of removing the etiologic agent/irritants, keeping the vulvar skin clean and dry as it repairs itself, initiating comfort measures as described previously, and applying low-potency corticosteroid cream to decrease pruritis and to break the itch/scratch cycle.

Iatrogenic Lesions

Multiple medical therapies can result in vulvar ulceration. These include condyloma treatment with keratolytic agents (podophyllin), laser, imiquimod, or fluorouracil; medication reaction; radiation; and poorly healing vulvar biopsy or surgical procedures. The cause of these lesions is almost always readily apparent from history and observation. Treatment consists of cessation of the inciting agent or treatment, comfort measures, and diligent hygiene. Lesions that do not heal must be evaluated for possible malignancy.

Irritants and Contact Dermatitis

An extremely wide range of items can cause an inflammatory skin reaction to the vulva, either due to immunologic reactions or simple chemical trauma. The list of these items includes-but is not limited to-chemicals in soaps, personal hygiene products, or laundry detergents; latex in medical gloves or condoms; metals such as nickel and copper in jewelry; plant resins and oils; and depilatories.

A prime example of such contact dermatitis is vulvar contact with urushiol, an oleoresin found in plants of the Anacardiaceae family in North America: poison ivy, poison oak, or poison sumac.10 The cause, pathophysiology, and treatment of other sources of contact dermatitis are in large measure the same as for urushiol dermatitis.

Contact with urushiol resin can occur by sitting, lying on, or brushing past vegetation where poison ivy is present. Such contact is especially common in warm weather when individuals wearing shorts or a bathing suit are exposed to brush in which poison ivy is growing. Poison ivy dermatitis can also be acquired secondarily, through contact with others who have been exposed to the oil, from pets, by touching garden tools with urushiol oil on them, or even by smoke inhalation of the vaporized oil when poison ivy is burned with other brush. It is estimated that 50% to 75% of the US adult population is sensitized to poison ivy, oak, and sumac.11

Skin reaction to poison ivy is a type IV hypersensitivity allergic reaction (ie, cell rather than antibody-mediated). The resulting skin lesions are almost always extremely pruritic and will consist of erythematous papules or confluent rashes, vesicles, and sometimes larger bullae. These lesions will often appear in longitudinal streaks reflecting the brush-by nature of contact with the responsible plant. The contacted tissues may swell; this can be especially apparent in the labia of women and the scrotum in men. The lesions develop relatively quickly, within hours to a few days after contact. Treated or not, the lesions persist for 1 to 2 weeks although the severity of symptoms can be minimized by treatment.

Treatment

The treatment of vulvar poison ivy consists of 4 key steps. First, as much of the plant oil as possible should be removed by thorough washing with hot water and soap or dish washing detergent. Rapid removal of the majority of the contacted material-within minutes or even several hours-can significantly reduce skin reaction. Any washing, even without soap, is beneficial. Similarly, any clothes, pets, or objects (tools, camping gear, etc) that have come into contact with the offending plant should be washed thoroughly. Second, the pruritis should be treated with menthol or phenol containing creams or lotions (eg, calamine). Oral antihistamines can help relieve itching. Third, comfort measures should be initiated as previously described. Finally, in more symptomatic cases, treatment with corticosteroids may be necessary. High-potency topical corticosteroids can be used for treating skin lesions before the vesicular stage.12 Efficacy of topical corticosteroids can be potentiated by occlusion and by the use of ointments rather than creams.13 Systemic corticosteroids can be used for severe reactions, those causing significant generalized swelling, or those involving the mouth or genitals that interfere with the ability to eat or void.

Allergic Dermatitis: Reactions to Topical and Systemic Medications

Rashes, vesicles, and ulcers caused by allergic reactions to specific medications are visually similar to those of contact dermatitis and largely respond to the same treatments (Figure 3).

Figure 3. Typical appearance of allergic dermatitis. (From Johnson et al,

These reactions are T-cell (type IV) immune reactions mediated by macrophages, eosinophils, and neutrophils.14 There is often a genetic predisposition to drug reactions. Medications commonly associated with drug reactions are listed in Table 1.

Table 1. Medications That Commonly Cause Drug Reactions

The diagnosis of a vulvar reaction due to medication allergy is generally made by history, specifically the timing of the lesions in relationship to drug intake, and by the visual appearance of the lesion or rash. There are no specific laboratory tests to aid in diagnosis. The treatment approach is to stop the offending medication and follow the same therapeutic steps as described for contact dermatitis.

Herpes Zoster

Herpes zoster is caused by a reactivation of the same varicella-zoster virus that causes chickenpox. Herpes zoster often begins with skin-tingling or burning similar to that experienced by those with herpes simplex recurrences. The prodrome is followed by a painful erythematous rash and multiple vesicles limited to a single unilateral dermatome (Figure 4). Vesicles continue to appear over several days. Once deroofed, they may combine to form larger plaques of denuded skin. Although most commonly seen on the trunk, herpes zoster can appear on the face, head, and vulva or male genitalia. Episodes involving the eyes are of special concern. Major symptoms can include moderate to severe pain in the affected area, pruritis, fever, and fatigue. The lesions eventually dry and crust over and may form scars. Postrecurrence neuralgia can also be a longer-term problem.

Figure 4. Vulvar vesicles of herpes zoster.

The diagnosis of zoster is made by visual examination, location in a single dermatome on one side of the body, history of chickenpox, and, if necessary, viral culture, immunofluorescent staining, or PCR testing. The vesicles have to be differentiated from bullous pemphigoid lesions, which are discussed in Part II of this series. Confusion can also arise in patients with these symptoms whose lesions are due to herpes simplex infections.

Vulvar herpes zoster should be treated with pain relievers and antiviral therapy to promote healing of cutaneous lesions and to decrease the pain and associated symptoms of acute neuritis. Antiviral therapy for herpes zoster employs the same medications as used with herpes simplex infections but in higher doses:

* Acyclovir: 800 mg 5 times daily for 7 days; or

* Famciclovir: 500 mg 3 times daily for 7 days; or

* Valacyclovir: 1000 mg 3 times daily for 7 days.17,18

Conclusion

Vulvar ulcers in girls and women are conditions that every gynecologist in general practice will see. As always, a careful history and physical examination are vital and may quickly make the diagnosis clear. Appropriate testing should be performed to confirm the diagnosis when possible. Comfort and hygiene measures will almost always be necessary along with other treatments such as antiviral medications or corticosteroids. Instructions will also have to be given to patients to contact their sexual partners, urging them to be evaluated and/or treated.

In addition to the pain and discomfort that vulvar ulcerative lesions cause, there is usually a tremendous emotional overlay on the part of patients who fear-correctly or not-that they have a sexually transmitted disease that will recur repeatedly, destroy their intimate relationships, and potentially interfere with future pregnancies. Therefore, in treating patients with vulvar ulcers, clinicians need to be especially sensitive to the emotional distress their patients may be experiencing.

Practice Pearls

* Herpes simplex I and II are by far the leading causes of painful vulvar ulcers a clinician will see in general practice.

* History and physical examination will lead to the diagnosis of most causes of vulvar ulcers. Subsequent testing usually plays only a confirmatory role.

* Always ascertain whether a patient presenting with vesicular, bullous, or ulcerative lesions has had them previously on other parts of her body.

* Treatment for all vulvar ulcer conditions includes comfort measures-soaks, analgesics, and often corticosteroid creams or ointments-even before more specific therapies are initiated.

* Clinicians must be sensitive to the emotional needs of patients experiencing vulvar ulcers.

References