INTRODUCTION — A wide variety of lesions occurs on the vulva. Some of the disorders causing these lesions are limited to the vulva, while others also involve skin or mucocutaneous membranes elsewhere on the body. This topic provides a morphology-based classification system that can help clinicians with the differential diagnosis of these lesions after performing a history and physical examination. This classification system is also useful for guiding the choice of diagnostic tests and procedures.
This topic will focus on the differential diagnosis of vesicles, bullae, erosions, and ulcerative vulvar lesions. Discussions of other pigmented lesions are presented in related content.
●(See "Vulvar lesions: Differential diagnosis of red lesions".)
●(See "Vulvar lesions: Differential diagnosis of white lesions".)
●(See "Vulvar lesions: Differential diagnosis of yellow, skin-colored, and edematous lesions".)
●(See "Vulvar lesions: Differential diagnosis of pigmented (black, brown, blue) lesions".)
The pertinent history, physical examination, and diagnostic tests and procedures used to evaluate patients with vulvar lesions are described separately (see "Vulvar lesions: Diagnostic evaluation"). Treatment is also discussed separately in topic reviews on these disorders.
In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. However, we encourage the reader to consider the specific counseling and treatment needs of transgender and gender diverse individuals.
MORPHOLOGIC DEFINITIONS FOR MUCOCUTANEOUS VULVAR LESIONS — Mucocutaneous vulvar lesions can be classified using the morphologic definitions described in the table (table 1).
DIAGNOSTIC EVALUATION
Practical tips — Based on the authors' experience, clinicians should be aware of the following points when evaluating dermatologic lesions of the vulva:
●Alternate appearance of vulvar lesions – Many skin conditions may appear differently on the vulva than on other parts of the skin as the vulva is so moist and the area is commonly subject to friction.
●Concomitant conditions – On the vulva, concomitant conditions are commonly present (eg, irritant contact dermatitis from the use of caustic soaps or over washing is commonly seen in individuals with vulvar lichen sclerosus).
●Impact of topical therapies – Vulvar conditions may be significantly altered by the use of topical treatments. The authors ask patients about use of prescription, over-the-counter, compounded, and alternative topical preparations.
●Role of biopsy – Be prepared to perform a biopsy, especially if a vulvar lesion is atypical, bleeding, the patient is immunocompromised, the lesion is not responding to appropriate treatment, or there is concern for a malignancy [1]. For any lesions with variable or irregular areas, more than one biopsy may be needed. At times, the biopsy results can be inconclusive. If there are ever concerns or questions about the biopsy report, it is important to speak with the pathologist.
●Consider possibility of systemic disease – Vulvar lesions can represent diseases that commonly present on the vulva (eg, herpes simplex virus) or systemic diseases that manifest in multiple sites including the vulva (eg, psoriasis). Providers are encouraged to ask patients with vulvar lesions about generalized symptoms and presence of lesions or skin changes on other body parts.
●Specialist referral – Patients whose symptoms do not respond, or worsen, despite usual treatment should be referred to a gynecologist, dermatologist, family medicine physician, or other health care providers who specialize in vulvar skin disorders.
How to use this topic — After a history, physical examination, and morphologic classification (table 1) have been performed, the information in this topic can be used to begin a differential diagnosis of the lesion. Diagnostic entities are listed for each morphologic classification and often listed under more than one morphologic classification since many lesions have more than one presentation (morphologic type, color). The complete description of the diagnostic entity is provided only once; for morphologic variants, the entity is noted and linked to its descriptive section.
This topic is an overview of vesicles, bullae, erosions, and ulcers of the vulva. Detailed text specific to each type of vulvar lesion is available separately, and links are provided throughout the text where available. Brief summaries of pertinent history, physical examination, and diagnostic tests and procedures are provided in this topic. Discussions of the presentation, evaluation, and diagnosis of vulvar lesions are described in detail separately.
●(See "Vulvar lesions: Diagnostic evaluation".)
●(See "Approach to the clinical dermatologic diagnosis".)
●(See "Skin biopsy techniques".)
VESICLES AND BULLAE — Vesicles are small (<1 cm) fluid-filled blisters while bullae are large (>1 cm) fluid-filled blisters (table 1). Both typically contain clear fluid. A differential diagnosis for vesicles and bullae specific to the vulva is presented in the table (table 2) [2]. An approach to the differential diagnosis of cutaneous blisters of all types is also available (algorithm 1).
Common etiologies — While the processes below are common causes of vulvar erosions, the relative frequency of each may vary based on the patient population and type of clinical practice (gynecology, internal medicine, or dermatology). Diagnosis is typically made with a combination of patient history and physical examination, although clinical testing for herpes simplex virus (HSV) may be needed for definitive confirmation.
Herpes simplex virus — A detailed discussion of the clinical manifestations and diagnosis of genital HSV is presented elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection".)
A brief summary follows:
●Clinical presentation – Genital HSV can present in either of two ways. The rarely encountered primary episode occurs with widespread genital vesicles, pustules, and/or erosions in a patient who is also experiencing fever, malaise, and dysuria (picture 1). The much more common recurrent form of genital herpes presents with 5 to 15 small (1 to 5 mm) vesicles that rapidly become pustular and contain clear then yellow fluid (picture 2). These are clustered over an area of approximately 2 to 5 cm. The vesicles/pustules quickly break, forming superficial, well-demarcated, round erosions on the skin, mucous membranes, and modified mucous membranes of the vulva. Swelling of the underlying skin is variable. A typical prodrome of localized itching, burning, or tingling supports the diagnosis. Eighty percent of individuals with herpes are unaware of their diagnosis. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Clinical features'.)
A clinical diagnosis of eroded genital herpes is usually possible based on the presence of collar-like scale around the circumference of the erosions, tight grouping of the erosions, a gyrate (ie, wavy) border if the erosions have become confluent, and a history of preceding, similar lesions at the same site. However, if this is the first outbreak, confirmation of the clinical diagnosis should be obtained.
●Diagnostic tests – Confirmation is most commonly achieved by polymerase chain reaction (PCR) technique-based testing. Viral cell culture and immunofluorescence testing are other test methods. The material is gently swabbed or scraped from the base of the erosion and spread onto a microscope slide; however, the sensitivity of viral culture is low, especially with recurrent HSV. HSV tests become negative approximately five days after the erosions have developed. Confirmation of HSV in erosions older than five days is difficult, if not impossible. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection".)
●Differential diagnosis
•Herpes zoster vesicles are almost identical in appearance to those of HSV. However, the clusters of vesicles and pustules are usually arranged in a dermatomal pattern and usually appear for the first time in older individuals. Appreciable pain occurring in the involved dermatome is also regularly present and usually precedes the outbreak of lesions by several days.
-(See 'Herpes zoster' below.)
-(See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster".)
•Candidiasis is more superficial, the lesions are pustules rather than vesicles, and the lesions are smaller in size and more numerous than those seen with HSV outbreaks. The broken pustules can be scattered or become confluent, forming a desquamating border. (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Candidiasis'.)
•Bullous impetigo is more superficial, with vesicles and bullae that break and form desquamating edges and honey-colored crusted lesions. (See 'Bullous impetigo' below.)
●HSV in immunosuppressed patients – HSV is the most common cause of vulvar ulcers in immunosuppressed patients. A diagnosis of HSV should be considered in all immunosuppressed women with nonhealing, usually painful, at times raw or necrotic-based ulcers with crusted edges (especially if a gyrate configuration is present); there may not be a history of a vesicular stage. In some instances, there is no appreciable pain. Because of the inability to muster a suitable immune response, the ulcers may persist for weeks to months and can gradually spread peripherally. The typical vesiculopustular, herpetiform, grouped HSV lesions may be seen at the edge of the expanding ulcers. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Immunosuppressed patients'.)
If diagnostic studies are negative, serologic tests for syphilis should be obtained, and biopsy should be performed to rule out aphthous ulcers, chancroid, pyoderma gangrenosum, and ulcerated malignancy. (See 'Acute vulvar aphthous ulcers' below and "Chancroid" and 'Rare' below.)
Herpes zoster — Herpes zoster is a vesicular skin eruption caused by reactivation of latent varicella-zoster virus (VZV) infection.
●(See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster".)
●(See "Treatment of herpes zoster in the immunocompetent host".)
Briefly:
●Clinical presentation – A burning- or tingling-type of pain is the first sign of herpes zoster. It starts in one area and spreads, usually unilaterally, along the involved dermatome(s). Systemically, there may be fever and malaise. On the skin, herpes zoster presents as round-to-oval edematous pink plaques unilaterally along a dermatome, with varying degrees of pain (picture 3 and picture 4) [3]. Within a day or two, groups of one to five vesicles appear on the surface of the red plaques (picture 5). These can become pustular. Groups of lesions erupt over several days. The vesicles often coalesce into larger bullae that may be purpuric. In the anogenital region, the blisters usually extend unilaterally along the buttocks to the labia majora and minora. The blister roofs break down quickly and easily, leaving painful, open, grouped erosions (3 to 7 mm). There can be loose scale (collarette or collar-like scale) at the periphery of the erosions. Occasionally, the lesions become confluent, leaving larger erosions possessing a gyrate configuration. The erosions crust over then heal. There can be ulceration and scarring. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Common findings'.)
●Diagnosis – A diagnosis can usually be established clinically based on the morphology. However, viral culture, immunofluorescent, or PCR-based identification may be desirable, considering that approximately 10 percent of the patients with the above morphology turn out to have HSV infection, rather than VZV infection. (See "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Approach to diagnosis'.)
●Differential diagnosis – The differential diagnoses include HSV, bullous impetigo, and bullous pemphigoid. HSV is usually more limited and often crosses the midline, while herpes zoster is classically unilateral along a dermatome. Bullous impetigo has thin-walled vesicles and bullae, which are culture positive for Staphylococcus aureus. Bullous pemphigoid has firm, thick-walled bullae. Neither condition is as painful as herpes zoster.
Bullous impetigo — Impetigo is a superficial bacterial infection; the bullous type is usually caused by S. aureus and less often by streptococcal species. The lesions initially consist of thin-walled, fragile vesicles and bullae. These break down quickly, leaving round erosions with collarettes of scale and variable honey-colored crusting (picture 6). Anogenital impetigo occurs on the keratinized skin of the labia, labiocrural folds, upper inner thighs, and mons pubis. Occasionally, the vesicles and bullae remain intact for several days, and when this occurs, the gradual accumulation of white blood cells results in yellow-white blister fluid. In addition to vesicles and bullae, one or more follicular red papules or pustules (bacterial folliculitis) are also often present. (See "Impetigo", section on 'Bullous impetigo'.)
Bullous impetigo can be confused with blistering diseases since the erosions in all of these diseases have well-demarcated, superficial peeling edges. Diagnosis is made through the recovery of S. aureus or streptococcal species on culture from the blister fluid or from the surface of the erosion that occurs after the blister roof is gone. (See "Impetigo".)
Less common etiologies — While the diseases below present with varying frequency, they are less common causes of vulvar vesicles and bullae (table 2).
Erythema multiforme — Erythema multiforme is an immune-mediated hypersensitivity reaction of the skin that can result from infections such as HSV or medication. It presents acutely as flat-topped, red papules and plaques that have been described as target lesions (picture 7A-H) and often follows a prodrome of fever and malaise. Typically, these lesions are seen on hands and feet and spread to the trunk. There are red macules that become raised, forming plaques that darken in the center and blister and crust over in two to three days. They are target-like with three zones: center dusky red that can blister and erode; swollen and pink middle ring; and the red outer edge. These lesions may coalesce to form generalized redness, covering up to 10 percent of the skin surface. Vesicles and bullae develop, as described, on the reddened skin as well as on all mucosal surfaces, including the vulva and vagina. These blisters break down very quickly to form painful erosions with serous and hemorrhagic crusting. The mucosal erosions frequently heal with scarring. The diagnosis is made by the typical clinical presentation of the prodrome, the pattern of the skin eruption, and the disorder's rapid progression. A skin biopsy may be required.
●(See "Erythema multiforme: Pathogenesis, clinical features, and diagnosis".)
●(See "Erythema multiforme: Management".)
Erythema multiforme is usually considered as separate from Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Contact dermatitis — Contact dermatitis is in the differential diagnosis of red patches and plaques (table 3), but itchy vesicles and bullae may occur following acute, usually allergic contact. (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Allergic contact dermatitis'.)
Rare etiologies — The following etiologies are rare causes of vulvar vesicles and bullae (table 2). Biopsy confirms these diagnoses.
Autoimmune blistering diseases — The diseases below represent rare blistering diseases of an autoimmune etiology. The vulva is one of many affected locations. As such, providers should ask about lesions elsewhere in patients suspected of having one of these processes. The approach to the patient with blistering disorders is presented separately. (See "Approach to the patient with cutaneous blisters".)
Bullous pemphigoid — This is an autoimmune blistering disease of older adults over 60 years of age. It presents as a generalized blistering eruption that rarely affects the keratinized skin of the vulva. The typical bullae can be seen on normal-looking or reddish skin. The presentation is polymorphous and includes a mixture of erosions (picture 8), red papules and plaques (picture 9), vesicles, and bullae (picture 10). The bullae are thick-walled, tense, unilocular, and filled with straw-colored or hemorrhagic fluid. When they rupture, they become serosanguineous crusted erosions that heal without scarring. Itching is usually severe. Clinical presentation, diagnosis (including directed biopsies, histology, and immunofluorescent staining), and differential diagnosis are reviewed in detail elsewhere.
Pemphigoid gestationis (herpes gestationis) — Pemphigoid gestationis (herpes gestationis) is an autoimmune blistering skin eruption that occurs in the second or third trimester of pregnancy. The clinical presentation is typically rapid onset of extremely itchy, red plaques on which vesicles and bullae develop. The blisters are very similar to those found in conventional pemphigoid, but the distribution in pemphigoid gestationis shows a marked predilection for the abdominal region (picture 11), especially the area around the umbilicus (picture 12). The vulva is not usually involved. The diagnosis is suggested by the associated pregnancy and clinical pattern, but it should be confirmed with biopsies submitted for conventional histology and direct immunofluorescence. (See "Dermatoses of pregnancy", section on 'Pemphigoid gestationis'.)
Pemphigus vulgaris — Pemphigus vulgaris is the most common of the pemphigus blistering disorders [4]. Typically, it presents on the mucous membranes of the mouth and genital area. Weeks or months later, it may involve the skin; although, in some cases, it may be limited to the mucous membranes. The blisters are thin-walled and rupture easily; patients typically present with resultant painful erosions that have mixed degrees of crusting. The vulva and the vagina can be affected with erosions and scarring, resulting in variable resorption of the labia minora, clitoral hood, and stenosis of the vagina (picture 13) [5]. The clinical presentation, diagnostic evaluation, and differential diagnosis are reviewed in separately. (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus".)
Cicatricial pemphigoid (mucous membrane pemphigoid) — Cicatricial pemphigoid (benign mucous membrane pemphigoid) is a mucosal blistering disease that is characterized by erosions and scarring of the mucous membranes of the eyes, mouth (picture 14 and picture 15 and picture 16), and genitalia in middle-aged patients. The usual presentation is painful erosions on the vulvar and vaginal mucous membranes that result in resorption of the labia minora, adhesions, and scarring. Diagnosis is made by routine histopathology and the direct immunofluorescent pattern. Cicatricial pemphigoid of the vulva and vagina must be differentiated from pemphigus vulgaris, erosive lichen planus, erosive lichen sclerosus, and SJS (table 4). (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Clinical features of mucous membrane pemphigoid'.)
Other
●Fixed drug eruption – Fixed drug eruption is a localized drug hypersensitivity that presents as red, brawny, or brown patches that can blister or erode, leaving postinflammatory hyperpigmentation (picture 17 and picture 18 and picture 19). Single or multiple lesions may develop on the vulva. Rarely, bullae can be seen. Characteristically, when the patient takes the same drug in the future, the lesion recurs at the same location. Diagnosis is suggested clinically and is confirmed by biopsy. (See "Fixed drug eruption".)
●Hailey-Hailey disease – Hailey-Hailey disease [6] and the related papular acantholytic dyskeratosis [7] usually present as red patches and plaques, often with varying degrees of erosion (picture 20 and picture 21 and picture 22 and picture 23). These lesions mimic the appearance of those described for extramammary Paget disease. However, if there is significant hyperkeratosis, the surface of the lesion may appear white when moist. Hailey-Hailey disease first appears in younger women, and there are almost always similar plaques on the chest, back, and axillae and a positive family history for similar lesions. Intact vesicles are rare. Papular acantholytic dyskeratosis, also rare, presents in both younger and older females. Biopsy is required for diagnosis. (See "Hailey-Hailey disease (benign familial pemphigus)".)
●Lymphangioma/lymphangiectasia – The closely set, nonfragile, dilated lymphatic vessels (pseudo-vesicles) in lymphangioma/lymphangiectasia arise on the surface of the skin, either from a hamartomatous skin defect (lymphangioma circumscriptum) or secondary to an obstruction of the lymphatics as a result of pelvic tumor radiation therapy, pelvic surgery, or severe inflammatory disease. These grouped vesicles are most often found on the mons pubis and labia majora. Underlying lymphedema is generally present. A clinical diagnosis can be confirmed by biopsy.
●Bullous lichen sclerosus – Rarely, lichen sclerosus can be bullous instead of the usual white patches and plaques (table 5). The bullae form on the usual white plaques associated with the disorder. They easily break, leaving erosions. The diagnosis is made clinically by the typical pattern of white skin and scarring or by biopsy.
•(See "Vulvar lesions: Differential diagnosis of white lesions", section on 'Lichen sclerosus'.)
•(See "Vulvar lichen sclerosus".)
●Other autoimmune conditions
•SJS and TEN – SJS and TEN are variants of the same rare syndrome. They are acute, serious, possibly fatal reactions to medications. SJS involves <10 percent of the skin surface and TEN >30 percent of the skin surface. They start with a flulike prodrome with fever, malaise, sore throat, and then the skin eruption. There is sudden onset of widespread, painful reddening of the skin over the trunk that spreads to the face and groin. These areas become vesiculobullous, and the lesions rapidly fuse with variably sized areas of skin detachment (picture 24 and picture 25 and picture 26). The skin quickly develops large, very painful, eroded areas (picture 27). The vulva and vagina can be diffusely involved. Lesions involving the vulva always present as erosions. Diagnosis is suggested by a history of medication use (especially the sulfa-related antibiotics), the presence of lesions elsewhere on the skin and other mucous membranes, and appreciable systemic toxicity. Diagnosis can be confirmed by relevant history, typically of drug exposure, and biopsy.
•Linear immunoglobulin A (IgA) bullous dermatosis and epidermolysis bullosa acquisita (EBA) – Linear IgA bullous dermatosis (linear IgA disease) and EBA are both rare autoimmune blistering diseases that can cause vulvar lesions.
-Linear IgA disease is characterized by the linear deposition of IgA at the dermoepidermal junction. (See "Linear IgA bullous dermatosis".)
-EBA is a rare, sporadic, subepithelial, mucocutaneous blistering disease that usually develops in adulthood. (See "Epidermolysis bullosa acquisita".)
EROSIONS, EXCORIATIONS, AND FISSURES — Erosions are shallow defects limited to the epidermis that heal without scarring (table 1). Excoriations are erosions caused by scratching. By contrast, ulcers are deeper lesions that extend through the whole epidermis into the dermis and heal with scarring (see 'Ulcers' below). Differential diagnosis for vulvar erosions is presented in the table (table 6).
Common causes — While the processes below are common causes of vulvar erosions, excoriations, and fissures, the relative frequency of each may vary based on the patient population and type of clinical practice (gynecology, internal medicine, or dermatology). Diagnosis is typically made with a combination of patient history and physical examination, although biopsy or clinical testing for infection may be needed for definitive confirmation of some etiologies.
Excoriation — Excoriation describes superficial, often linear, skin erosions caused by scratching (picture 28). Patients are usually aware of their scratching. However, it sometimes only occurs during sleep, and patients may be unaware that they are causing the erosions. Scratching most often occurs with lichen simplex chronicus and atopic dermatitis but can be superimposed on other disorders, notably lichen sclerosus, candidiasis, tinea cruris, and psoriasis (table 3 and table 5). The diagnosis of excoriation is established clinically. Much more rarely, patients gouge, pick, and/or dig at their skin, causing ulcers rather than erosions. (See "Skin picking (excoriation) disorder and related disorders".)
Fissures — Fissures are narrow splits/cracks or linear erosions in the epidermis. Vulvar fissures present in two patterns: posterior fourchette fissures and fissures within skinfolds and skin creases.
Posterior fourchette fissures — Posterior fourchette fissures are primary fissures that arise de novo on previously normal-appearing skin. They can occur in the midline of the posterior fourchette after vaginal penetration or coitus.
Some women, usually premenopausal, develop painful, chronically recurring fissures at the posterior fourchette from physical trauma at penetration or later on during sexual intercourse [8,9]. These fissures perpendicularly cross the folded tissue of the fourchette at 6 o'clock and vary in width from a hairline crack to a linear defect that is several millimeters wide.
The diagnosis is established clinically based on the history of a painful fissure developing at, or shortly after, penile intromission. No other causes of skin inflammation are seen. Since many of these women do not carefully examine themselves, it may be necessary to have the patient appear in the office on the day of, or the day after, painful intercourse to determine that a fissure is present. This will distinguish between postcoital fissure and entrance dyspareunia and provoked vestibulodynia.
●(See "Vulvar pain of unknown cause (vulvodynia): Clinical manifestations and diagnosis".)
●(See "Female sexual pain: Evaluation".)
Skinfold fissures — Skinfold fissures are a secondary skin phenomenon that can occur in response to infection or dermatoses [8].
●Candidiasis – Vulvar candidiasis may present solely with red eczematous plaques (table 3). While pustules are commonly present, the severity of pruritus, with consequent scratching, results in breakage of the pustules (table 7) and scattered erosions. Skinfold fissures are common and typically seen in the interlabial sulci. Excoriations can be seen, and, if severe, there can be an ulcerative presentation instead of erosions (table 3). (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Candidiasis'.)
●Herpes simplex virus (HSV) – Because the vesicles of HSV are very fragile, many patients present with erosions rather than blisters. At times, small fissures may be seen. (See 'Herpes simplex virus' above.)
●Lichen simplex chronicus – The red patches and plaques of lichen simplex chronicus are almost always characterized by the presence of excoriations and, at times, fissures and erosions (picture 29). (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Lichen simplex chronicus'.)
●Erosive lichen sclerosus – Erosions frequently develop in lichen sclerosus, which more commonly presents as white patches or plaques. Because basement membrane damage (inherent in the disease) allows easy separation of the epidermis, minimal trauma causes erosions. Erosions also may result from rubbing or scratching or develop on the surface of nodules and plaques of underlying squamous cell carcinoma (SCC).
•(See "Vulvar lesions: Differential diagnosis of white lesions", section on 'Lichen sclerosus'.)
•(See "Vulvar lichen sclerosus".)
Erosive lichen planus — The erosive form of lichen planus is the most common presentation and does not usually coexist with the papulosquamous form of the disorder (table 3) [10]. It causes a significant burden with its symptoms and sequelae [11]. The erosions are found in the vestibule, most commonly between 4 and 8 o'clock, and may extend into the vagina (picture 30 and picture 31) [10]. These erosions often have a glazed red surface. They are extremely painful and can often be extensive. Scarring often develops and can result in entrapment of the clitoris, effacement of the labia minora, and vaginal narrowing or even occlusion (picture 32). (See "Vulvar lichen planus", section on 'Erosive vulvar lichen planus'.)
Rarely, vulvar lichen planus can be very itchy and associated with scratching and resultant excoriation. Clinical diagnosis is possible if the lacy white changes are found peripheral to the erosions and/or if the same white lesions are found in the mouth. If these lesions are not present, biopsies should be considered. One biopsy is taken at the edge of the erosion and sent for histopathologic testing, and the other biopsy is taken from normal-appearing skin adjacent to the margin of the erosion and sent for immunofluorescent studies. Vulvovaginal lichen planus can rarely be associated with SCC, and it can present with an eroded surface [12]. (See "Vulvar lichen planus", section on 'Biopsy'.)
Impetigo — The initial lesions in impetigo are often pustules, vesicles, or bullae (table 2). However, the roofs of these lesions are extremely fragile, often leading to a presentation with erosions. (See 'Bullous impetigo' above.)
Irritant contact dermatitis — The primary appearance of irritant contact dermatitis is eczematous (table 3), but sometimes, erosions or even linear fissures are prominent. (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Irritant contact dermatitis'.)
Trauma (physical and chemical) — There are many potential traumatic causes of vulvar erosions, both physical and chemical.
●Physical – Causes include blunt or sharp trauma, surgery, radiation, pressure, excessive heat or cold (cryotherapy), laser treatment, and vaginal penetration (ie, posterior fourchette fissures). (See 'Posterior fourchette fissures' above.)
●Chemical – Causes include exposure to antiseptics, destructive medications like bichloracetic and trichloroacetic acid, 5-fluorouracil, and 20% benzocaine. These causes are usually easily identified on history.
Less common causes — While the processes below are not necessarily uncommon causes of erosions, they less commonly present as erosions of the vulva (table 6). Diagnosis is typically made with a combination of history and physical examination, but biopsy may be necessary to exclude other etiologies. Fragile vesicles and bullae can rupture easily and appear as erosions rather than blisters at the time of physical examination (table 2). These erosions are commonly seen with the following conditions.
Allergic contact dermatitis — The primary appearance of allergic contact dermatitis is eczematous, but itching and scratching often result in excoriations. Vesicles and blisters can result in erosions. (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Allergic contact dermatitis'.)
Erosions following vesicles or bullae — Fragile vesicles and bullae can rupture easily and appear as erosions rather than blisters at the time of physical examination (table 2).
●Herpes zoster – The vesicles of herpes zoster may become unroofed by the time the patient is examined and appear as erosions (table 2). The history of pain and the dermatomal pattern help to make the diagnosis. (See 'Herpes zoster' above.)
●Erythema multiforme – Erythema multiforme is frequently associated with a mixture of bullae and erosions (table 2). (See 'Erythema multiforme' above.)
Eroded malignancy — As malignancy advances, the surface of the lesions erode (table 8) and, eventually, can ulcerate. (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Squamous cell carcinoma'.)
Rare causes — Hailey-Hailey disease, extramammary Paget disease, and toxic epidermal necrolysis usually present with red patches and/or plaques. As associated vesicles and bullae rupture, the clinical presentation can also include erosions.
●(See "Hailey-Hailey disease (benign familial pemphigus)".)
The blistering diseases (table 2) commonly have erosions of varying sizes that can be extensive, particularly with pemphigus vulgaris. (See 'Autoimmune blistering diseases' above.)
ULCERS — Ulcers are deep defects through the epidermis into the dermis that heal with scarring (table 1). They differ from erosions based on depth; erosions are shallow defects limited to the epidermis. In general, ulcerative lesions of the vulva are not common. The causes, grouped by estimated relative frequencies, are presented below (table 9). The prevalence of ulcerative lesions and their causes vary by geographic location. The authors begin their differential diagnosis of vulvar ulcerative lesions by considering relative disease prevalence and then evaluating for infectious and noninfectious etiologies within each category.
Detailed discussion of the approach to patients with genital ulcers is presented separately. (See "Approach to the patient with genital ulcers".)
Infectious — Although ulcerative vulvar lesions are uncommon overall, infection is a frequent cause when they do occur (table 9). The authors begin with the differential diagnosis groupings below but caution that the prevalence of both infectious and noninfectious etiologies varies by geographic region. (See "Approach to the patient with genital ulcers", section on 'Infectious etiologies'.)
●More common – Herpes simplex virus (HSV) in immunosuppressed patients and primary syphilis in any patient.
•HSV in the immunosuppressed – HSV infection is the most common cause of numerous or persistent vulvar ulcers in the immunosuppressed patient. Immunocompromised individuals present with well-demarcated, punched out, variably painful, nonhealing ulcers located anywhere on the vulva, perineum, and perianal areas. An ulcer can extend from the vulvar mucous membrane out onto the labia majora and back to the perineum. The ulcers are circular or arcuate with spreading borders and variable necrosis. Eroded or ulcerated papules or nodules may also occur. At the edges of the ulcer(s), the typical herpetiform pustules of HSV may be seen. (See 'Herpes simplex virus' above.)
•Primary syphilis – Primary syphilis presents as one or two usually painless ulcers (chancres), 1 to 2 cm in diameter (picture 33 and picture 34). These develop 10 to 90 days after exposure and last three to six weeks. The ulceration usually has a clean base, with little or no pus or crust. On palpation, the base of the ulcer feels firm. Regional lymphadenopathy may or may not be present. The clinical setting may be highly suggestive for primary syphilis, but the diagnosis must be confirmed by laboratory testing. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV" and "Syphilis: Screening and diagnostic testing".)
●Rare – Rare causes of vulvar ulcers include cytomegalovirus (CMV), HIV, granuloma inguinale (picture 35), chancroid, and lymphogranuloma venereum.
•CMV – (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults".)
•HIV – (See "Approach to the patient with genital ulcers", section on 'Sexually transmitted'.)
•Granuloma inguinale – (See "Approach to the patient with genital ulcers", section on 'Sexually transmitted'.)
•Lymphogranuloma venereum – (See "Lymphogranuloma venereum".)
•Chancroid – (See "Chancroid".)
●Very rare – Tuberculosis, amebiasis, schistosomiasis, and leishmaniasis are very rare causes of vulvar ulcers. (See "Approach to the patient with genital ulcers", section on 'Non-sexually transmitted infections'.)
Noninfectious
More common — While the processes below are more common causes of vulvar ulcers (table 9), the relative frequency of each may vary based on the patient population and type of clinical practice (gynecology, internal medicine, or dermatology). Diagnosis is typically made with a combination of patient history and physical examination.
Acute vulvar aphthous ulcers — Acute vulvar aphthous ulcers (also called acute genital ulceration, Lipschütz ulcers, ulcus vulvae acutum, reactive nonsexually related acute genital ulcers, nonsexually acquired genital ulceration [NSAGU], and vulvar aphthae) are similar to the much more common oral aphthous ulcers (canker sores) [13]. In approximately 30 percent of individuals, acute aphthous ulcers are associated with various infections; the most common are Epstein-Barr virus, Mycoplasma pneumoniae, and viral respiratory infections (parvovirus, influenza, paramyxovirus). These ulcers are the result of a localized vasculitis. (See "Acute genital ulceration (Lipschütz ulcer)".)
●Clinical presentation – The ulcers occur suddenly and are very painful. The first lesion is usually a purpuric area that rapidly becomes necrotic then ulcerated over one to two days. Patients generally present with multiple ulcers that are sharply marginated (punched out) and may have a white coagulum or adherent, black crust at the base of the ulcer (picture 36). In contrast to oral ulcers, vulvar ulcers are more likely to be large (up to 3 cm), may involve the skin as well as the modified mucous membranes of the vestibule, assume a gyrate configuration when two or more adjacent ulcers grow into confluence, and heal more slowly (over two or three weeks). (See "Acute genital ulceration (Lipschütz ulcer)", section on 'Clinical manifestations'.)
The majority of patients have flulike symptoms that precede or accompany the ulcers. They typically occur in girls and young women between the ages of 8 and 25 years, although the age range is infancy to middle age. Approximately one-half of the patients have had, or will develop, oral aphthous ulcers. Approximately one-third of the patients have had, or will develop, recurrent vulvar aphthous ulcers. (See "Recurrent aphthous stomatitis", section on 'Classification'.)
●Diagnosis – The diagnosis is based on the clinical findings and exclusion of other causes of vulvar ulcers. Polymerase chain reaction (PCR) testing to rule out HSV infection and tests to rule out syphilis and other causes of vulvar ulceration can be indicated if the clinician is uncertain. Biopsy is seldom indicated. (See "Acute genital ulceration (Lipschütz ulcer)", section on 'Diagnosis'.)
Trauma — Traumatic vulvar ulcers can be accidental or iatrogenic and caused by physical or chemical insult [14]. Diagnosis is generally based on history and physical examination.
●Accidental – Traumatic ulcers are characteristically linear or angular. The most common form of accidental trauma is deep excoriation (gouging), usually in the setting of lichen simplex but can also be seen in lichen sclerosus and severe irritant contact dermatitis. Chronic pressure in the wheelchair-bound patient can cause vulvar pressure ulcers on the upper vestibule. The duration of these ulcers may be intermittent or long term.
●Iatrogenic – Iatrogenic ulcers can develop after treatment with liquid nitrogen or the application of bichloracetic or trichloroacetic acid, imiquimod, or fluorouracil. A commonly missed chemical cause of vulvar ulcers is the use of topical 20% benzocaine. Iatrogenic physical causes also include surgery, radiation, and laser treatments.
Rarely, traumatic ulcers may be intentionally induced. (See 'Traumatic patient-induced vulvar ulcers' below.)
Less common — Less common causes of vulvar ulceration are presented below (table 9). Diagnosis is typically made with a combination of history, physical examination, and biopsy.
Malignancy — While squamous cell carcinoma (SCC) and melanoma are relatively common on other regions of the body, they can also present as vulvar ulcers (table 9). Vulvar cancers are the fourth most common gynecologic malignancy [15,16].
●SCC of the vulva – SCC is the most common subtype of vulvar cancer and represents approximately 75 percent of cases. Forty percent of the occurrences are associated with vulvar lichen sclerosus, particularly in patients with chronic and poorly controlled disease. Usually, there is a nodule or an eroded area that ulcerates. Ulcers can also be associated with SCC in association with oncogenic human papillomavirus. (See "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment".)
●Melanoma – Vulvar melanomas are the second most common form of vulvar cancer. They generally are black or dark brown in color (picture 37 and picture 38 and picture 39 and picture 40); however, amelanotic vulvar melanomas have been reported (picture 41). Providers use the ABDCE's (asymmetry; border irregularity; color changes; diameter greater than 6 mm; evolving size, shape, or color) of skin changes to determine if a biopsy is needed. (See "Melanoma: Clinical features and diagnosis".)
Crohn disease — Patients with Crohn disease often present with a mixture of inflammatory lesions (table 8), fissures, aphthous ulcers, and "knife-cut" ulcers (picture 42 and picture 43). Labial swelling is the most common presentation (60 percent), and 35 percent of these individuals can have vulvar ulcers. Classically, knife-cut ulcers are seen in the vulvar skinfolds, the interlabial sulci, beside the clitoral hood, on the perineum, and in the gluteal cleft. The aphthous ulcers of Crohn disease can also be seen anywhere on the vulva. These ulcers can be dramatic and may or may not be painful. The differential diagnosis of knife-cut ulcers includes Langerhans cell histiocytosis, HSV ulcers in the immunosuppressed, and granuloma inguinale. A diagnosis of Crohn disease is made on the clinical pattern, biopsy, and gastrointestinal workup.
●(See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Crohn disease'.)
●(See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)
Hidradenitis suppurativa — Hidradenitis suppurativa is a chronic, follicular, inflammatory skin condition that is also referred to as "acne inversus." Ulcerative lesions may rarely be present among the more typical red papules and inflammatory nodules and sinuses. (See "Vulvar lesions: Differential diagnosis of red lesions", section on 'Hidradenitis suppurativa'.)
Rare — The following are rare causes of vulvar ulcers (table 9); biopsy is typically required to confirm the diagnosis.
Other malignancies — Basal cell carcinoma, adenocarcinoma, and both non-Hodgkin and Hodgkin lymphoma can rarely cause ulcerative lesions that may appear on the vulva.
●(See "Epidemiology, pathogenesis, clinical features, and diagnosis of basal cell carcinoma".)
●(See "Adenocarcinoma of unknown primary site".)
Pyoderma gangrenosum — The initial lesion in pyoderma gangrenosum is usually a pustule or inflamed papule or nodule. These lesions quickly progress to one or more slowly enlarging, painful ulcers, which may be shallow or deep. Deep ulcers characteristically have a violaceous, overhanging, circumferential border.
A diagnosis may be suspected clinically, but bacterial and fungal cultures, as well as a biopsy taken from normal-appearing tissue at the edge of the ulcer, should be performed to rule out other forms of ulcers. This disease is idiopathic in half of affected patients. In the other half of affected patients, associated diseases include inflammatory bowel disease and hematopoietic malignancy. (See "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis".)
Langerhans cell histiocytosis — Langerhans cell histiocytosis is a histiocytic disorder that most commonly causes osteolytic bone lesions but can rarely cause vulvar ulcerations. These ulcers are usually single and can mimic the classic knife-cut ulcers of Crohn disease. A biopsy is needed for diagnosis. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis".)
Complex vulvar aphthous ulcers — Complex vulvar aphthous ulcers are ulcers on both the oral and genital mucosa. These are much less common than simple vulvar aphthous ulcers. They can be almost constant or one or more recurrent vulvar ulcers with or without oral aphthous ulcers that seldom occur at the same time. These are usually >1 cm and can be single or, usually, multiple. They last weeks to months and can scar. (See "Recurrent aphthous stomatitis", section on 'Complex aphthosis'.)
Chronic and acute aphthous ulcers have a similar appearance because they are nonspecific reactions rather than a direct manifestation of an associated disease. While chronic or recurrent aphthous ulcers are often idiopathic, they may be associated with inflammatory bowel diseases (Crohn disease [most common], ulcerative colitis), hematologic problems (myeloproliferative disorders, cyclic neutropenia, lymphopenia), Behçet syndrome, and, rarely, HIV infection. On rare occasions, medications may cause aphthous ulcers (eg, cytotoxic medications and nonsteroidal anti-inflammatory drugs).
●(See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)
●(See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)
●(See "Overview of the myeloproliferative neoplasms".)
●(See "Clinical manifestations and diagnosis of Behçet syndrome".)
Traumatic patient-induced vulvar ulcers — Occasionally, ulcers are induced in otherwise normal-appearing skin by psychologically dysfunctional individuals; these have been termed "neurotic excoriations." Rarely, ulcers are caused by intentional, but unacknowledged, self-induced trauma [14]. When this is encountered, it is usually related to genital self-cutting or in patients with delusions of bugs or fibers in their skin. A correct diagnosis may be suspected clinically, but psychiatric intervention will often be necessary. (See "Skin picking (excoriation) disorder and related disorders".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vulvar dermatitis".)
SUMMARY AND RECOMMENDATIONS
●Initial evaluation – For individuals with vulvar lesions, evaluation begins with a history, physical examination, and morphologic classification of the lesion (table 1), which allows formation of the differential diagnosis. (See 'Morphologic definitions for mucocutaneous vulvar lesions' above.)
●Clinical points – Based on the authors' experience, clinicians should be aware of the following points when evaluating dermatologic lesions of the vulva (see 'Practical tips' above):
•Alternate appearance of vulvar lesions – Many skin conditions may appear differently on the vulva than on other parts of the skin as the vulva is so moist and the area is commonly subject to friction.
•Concomitant conditions – On the vulva, concomitant conditions are commonly present (eg, irritant contact dermatitis from the use of caustic soaps or over washing is commonly seen in individuals with vulvar lichen sclerosus).
•Impact of topical therapies – Vulvar conditions may be significantly altered by the use of topical treatments. The authors ask patients about use of prescription, over-the-counter, compounded, and alternative topical preparations.
•Role of biopsy – Be prepared to perform a biopsy, especially if a vulvar lesion is atypical, bleeding, the patient is immunocompromised, the lesion is not responding to appropriate treatment, or there is concern for a malignancy. For any lesions with variable or irregular areas, more than one biopsy may be needed. At times, the biopsy results can be inconclusive. If there are ever concerns or questions about the biopsy report, it is important to speak with the pathologist.
•Consider possibility of systemic disease – Vulvar lesions can represent diseases that commonly present on the vulva (eg, herpes simplex virus [HSV]) or systemic diseases that manifest in multiple sites including the vulva (eg, psoriasis). Providers are encouraged to ask patients with vulvar lesions about generalized symptoms and presence of lesions or skin changes on other body parts.
•Specialist referral – Patients whose symptoms do not respond, or worsen, despite usual treatment should be referred to a gynecologist, dermatologist, family medicine physician, or other health care providers who specialize in vulvar skin disorders.
●Vesicles and bullae – Vesicles are small (<1 cm) fluid-filled blisters while bullae are large (>1 cm) fluid-filled blisters (table 1). Both typically contain clear fluid. A differential diagnosis for vesicles and bullae of the vulva is presented in the table (table 2). (See 'Vesicles and bullae' above.)
•Common etiologies include HSV, herpes zoster, and bullous impetigo. (See 'Common etiologies' above.)
•Less common etiologies include erythema multiforme and contact dermatitis. (See 'Less common etiologies' above.)
•Rare etiologies include autoimmune blistering diseases (eg, bullous pemphigoid, pemphigoid gestationis [herpes gestationis], pemphigus vulgaris, and cicatricial pemphigoid [mucous membrane pemphigoid]), fixed drug eruption, Hailey-Hailey disease, lymphangioma/lymphangiectasia, bullous lichen sclerosus, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), linear immunoglobulin A disease, and epidermolysis bullosa acquisita. (See 'Rare etiologies' above.)
●Erosions, excoriations, and fissures – Erosions are shallow defects limited to the epidermis that heal without scarring (table 1). Excoriations are erosions caused by scratching. By contrast, ulcers are deeper lesions through the dermis that heal with scarring (see 'Ulcers' above). The differential diagnosis for vulvar erosions is presented in the table (table 6).
•Common causes include excoriations from scratching, fissure (both posterior fourchette and skinfold fissures), erosive lichen planus, impetigo, irritant contact dermatitis, and trauma (both physical and chemical). (See 'Common causes' above.)
•Less common causes include allergic contact dermatitis, erosions that develop following vesicles or bullae (eg, herpes zoster infection, erythema multiforme), and eroded malignancy. (See 'Less common causes' above.)
•Rare causes of erosions include Hailey-Hailey disease, extramammary Paget disease, and TEN. While these processes usually present with red patches and/or plaques, the clinical presentation can also include erosions after the initial vesicles or bullae rupture. Autoimmune blistering diseases (table 2) commonly have erosions of varying sizes that can be extensive. (See 'Rare causes' above.)
●Ulcers – Ulcers are deep defects through the dermis that heal with scarring (table 1). They differ from erosions based on depth; erosions are shallow defects limited to the epidermis. In general, ulcerative lesions of the vulva are not common. The causes, grouped by estimated relative frequencies, are presented in the table (table 9).
•Infectious causes of vulvar ulcers include the more common HSV in the immunosuppressed patient and primary syphilis. The rare infectious causes include cytomegalovirus, HIV, granuloma inguinale, lymphogranuloma venereum, and chancroid. Very rare causes of genital ulcers include tuberculosis, amebiasis, schistosomiasis, and leishmaniasis.
•Noninfectious ulcers can be divided into more common, less common, and rare categories.
-More common causes include acute vulvar aphthous ulcers and trauma, both accidental and iatrogenic.
-Less common causes of vulvar ulcers include malignancy (squamous cell carcinomas and melanomas of the vulva), Crohn disease, and hidradenitis suppurativa.
-Rare noninfectious conditions include other malignancies, pyoderma gangrenosum, Langerhans cell histiocytosis, complex vulvar aphthous ulcers, and patient-induced trauma.
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Drs. T Minsue Chen, Aileen Langston, and Peter Lynch, who contributed to earlier versions of this topic review.
