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Acute genital ulceration (Lipschütz ulcer)

Acute genital ulceration (Lipschütz ulcer)
Literature review current through: Jan 2024.
This topic last updated: Aug 31, 2022.

INTRODUCTION — Acute genital ulceration, also known as "Lipschütz ulcer" or "ulcus vulvae acutum," is an uncommon, self-limited, nonsexually transmitted condition characterized by the rapid onset of painful, necrotic ulcerations of the vulva or lower vagina. It typically occurs in sexually inactive adolescent females or young females and may be preceded by influenza-like or mononucleosis-like symptoms [1]. Acute genital ulceration has been associated with acute Epstein-Barr virus (EBV) infection or other viral and bacterial infections [2-5]. However, in many cases a cause cannot be determined [6-8].

This topic will review the clinical manifestations, diagnosis, and management of acute genital ulceration. Other causes of vulvar ulceration are discussed separately. (See "Vulvar lesions: Differential diagnosis of vesicles, bullae, erosions, and ulcers", section on 'Ulcers' and "Approach to the patient with genital ulcers".)

EPIDEMIOLOGY — The precise incidence of acute genital ulceration is unknown. It occurs predominantly in adolescent females and young females, but there are reports of acute genital ulcerations in adult females and very young children [9-12]. In a systematic review of case reports and small case series that included 158 patients, nearly 90 percent of the patients were ≤20 years of age [13].

ETIOLOGY AND PATHOGENESIS — Several lines of evidence suggest that acute genital ulceration may be a manifestation of primary infection with Epstein-Barr virus (EBV) [2,6,13-16]. EBV might reach the genital mucosa via hematogenous spread of EBV-infected lymphocytes or Langerhans cell precursors or through autoinoculation with saliva, urine, or cervicovaginal fluid [3]. (See "Clinical manifestations and treatment of Epstein-Barr virus infection", section on 'Primary infection'.)

There are isolated reports of acute genital ulceration associated with infection with other viruses and bacteria, including cytomegalovirus [17], influenza A virus [18], influenza B virus [19], mumps virus [20], salmonella [21], mycoplasma [22-24], disseminated Lyme disease [25], and with group A Streptococcus [26]. Cases have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination [27-29]. In one report, genital ulcers were the first manifestation of acute myeloid leukemia in a 28-year-old woman [30]. In another case, acute vulvar ulcers were the first manifestation of Sjögren's disease [31]. However, in most cases, a cause cannot be determined [6-8].

The exact pathogenesis of acute genital ulceration is unclear. One hypothesis suggests that the ulcer is the clinical manifestation of a hypersensitivity reaction to a viral or bacterial infection, with deposition of immune complex in the dermal vessels, complement activation, microthrombosis, and subsequent tissue necrosis [16,32]. In a series of seven women who experienced acute vulvar ulceration during a serologically confirmed episode of active EBV infection and histopathologic finding of vasculitis in ulcer biopsies, latent membrane protein-1 immunohistochemical staining was positive in endothelial cells adjacent to ulcer and foci of vasculitis in six cases. In situ hybridization for EBV early mRNA (EBER) was positive in three specimens, in solitary or clustered lymphocytes, suggesting a host immunopathologic response rather than a lytic EBV infection of endothelial cells as the initial event in the pathogenesis of vulvar ulceration [33].

PATHOLOGY — The histopathologic findings in acute genital ulcerations are usually nonspecific and include necrosis of the epithelium with a polymorphic dermal infiltrate of neutrophils and CD8+ mononuclear cells [2]. Features of lymphocytic arteritis and venulitis, endarteritis obliterans, thrombosis, sebaceous adenitis, and a predominantly lymphocytic infiltrate have been found in women with acute genital ulceration and serologically confirmed acute infection with Epstein-Barr virus (EBV) [33].

CLINICAL MANIFESTATIONS — Patients are typically nonsexually active adolescent females or young females reporting the sudden onset of one or multiple vulvar ulcerations. Ulcers are usually large (>1 cm) and deep, with a red-violaceous border and a necrotic base covered with a grayish exudate or an adherent gray-black eschar (picture 1). Most often, ulcers involve the labia minora but can extend to the labia majora, perineum, vestibule, and lower vagina. A partially symmetrical appearance ("kissing lesions") is characteristic (picture 2). Associated signs include labial edema and inguinal lymphadenopathy.

Intense pain and dysuria are universal complaints.

Most patients report prodromal influenza-like or mononucleosis-like symptoms, including fever, malaise, tonsillitis, lymphadenopathy, and increased levels of liver enzymes. Some patients have a history of oral aphthosis and/or have concomitant oral lesions at the time of presentation [4].

The course of the disease is self-limited. Spontaneous healing of acute genital ulceration occurs in two to six weeks. (See 'Prognosis' below.)

DIAGNOSIS — Acute genital ulceration is a clinical diagnosis and one of exclusion. It is based upon detailed history and complete physical examination. Laboratory investigations may be necessary to exclude other causes of genital ulceration, including sexually transmitted diseases, Behçet syndrome, inflammatory bowel disease, and autoimmune bullous diseases. Evidence of acute Epstein-Barr virus (EBV) infection supports the diagnosis of acute genital ulcer in the setting of primary EBV infection [14]. (See 'Laboratory tests' below.)

Clinical diagnosis — The initial evaluation of the patient presenting with acute genital ulceration includes a thorough medical history and physical examination. The review of systems should include information about systemic illness, with particular attention to ocular, neurologic, gastrointestinal, and genitourinary symptoms.

A careful sexual history should also be taken, including questions on sexual activity and potential sexual abuse. In adolescents, assurance of confidentiality is an important aspect of obtaining an accurate sexual history. (See "Confidentiality in adolescent health care" and "Evaluation of sexual abuse in children and adolescents".)

A complete physical examination should include the skin; genital, oral, and ocular mucosa; and lymph nodes to exclude genital ulcerations secondary to other diseases. The presence of hepatosplenomegaly should also be assessed.

Proposed criteria for the clinical diagnosis of acute genital ulceration in an adolescent female or young female with a recent history of an influenza-like or mononucleosis-like illness include [2]:

First episode of acute genital ulceration

Age <20 years

Presence of one or multiple deep, well-delimited, painful ulcers with a necrotic base on the labia minora or labia majora (picture 1)

Bilateral, "kissing" pattern

Absence of any sexual history or absence of sexual contact in the previous three months

Absence of immunodeficiency

Acute course, with abrupt onset and healing within six weeks

Laboratory tests — Because genital herpes simplex virus (HSV) is the most common cause of genital ulceration, laboratory evaluation should include viral culture or, preferably, direct fluorescence antibody (DFA) test or polymerase chain reaction (PCR) for HSV from ulcer swabs. Microbiologic or serologic tests for other sexually transmitted genital ulcers (eg, syphilis, lymphogranuloma venereum, chancroid) are performed based upon history and clinical suspicion. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Diagnosis' and "Approach to the patient with genital ulcers", section on 'Diagnostic testing'.)

Serology for EBV is also indicated. Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies directed against the Epstein-Barr viral capsid antigen (VCA) are a good marker of acute infection; they are usually present at the onset of clinical illness and are detectable up to three months later. Serology for cytomegalovirus and Mycoplasma pneumoniae may be indicated in some patients, based upon history and clinical suspicion. A complete blood count with differential to assess for lymphocytosis and presence of atypical lymphocytes and liver function tests should also be performed. (See "Infectious mononucleosis", section on 'Diagnosis' and "Overview of diagnostic tests for cytomegalovirus infection" and "Mycoplasma pneumoniae infection in adults", section on 'Diagnosis'.)

Bacterial cultures from the ulcer exudate should be obtained in patients with clinical signs of bacterial superinfection or vulvar cellulitis.

Biopsy — Biopsy is typically unhelpful for the diagnosis of acute genital ulceration. However, a biopsy may be necessary if a specific skin disease is suspected (eg, pyoderma gangrenosum, autoimmune bullous diseases).

The histologic findings in biopsies of acute vulvar ulcers are often nonspecific and include necrosis of the epithelium with a polymorphic dermal infiltrate of neutrophils and CD8+ mononuclear cells [2]. However, in a series of seven women with acute vulvar ulceration during a serologically confirmed episode of active EBV infection, the most frequent findings were lymphocytic arteritis and venulitis, endarteritis obliterans, thrombosis, sebaceous adenitis, and a predominantly lymphocytic infiltrate [33]. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of acute genital ulcers is extensive and includes sexually transmitted infections (eg, herpes simplex virus infection, acute HIV infection, syphilis) and noninfectious causes of genital or orogenital ulcerations (eg, complex aphthosis, Behçet syndrome, autoimmune bullous diseases) (see "Approach to the patient with genital ulcers" and "Vulvar lesions: Differential diagnosis of vesicles, bullae, erosions, and ulcers", section on 'Ulcers'):

Genital herpes – Genital herpes typically presents with smaller and superficial erosions often coalescing in a polycyclic pattern (picture 3). Direct fluorescence antibody (DFA) test, polymerase chain reaction (PCR), or culture of specimens obtained from the genital lesions can confirm the diagnosis. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection".)

HIV infection – Painful mucocutaneous ulcerations is one of the most distinctive manifestations of acute HIV infection. Quantitative plasma HIV RNA (viral load) and HIV antibody testing should be performed to confirm the diagnosis. (See "Acute and early HIV infection: Clinical manifestations and diagnosis", section on 'Diagnosis'.)

Syphilis – The classic chancre of primary syphilis is a 1 to 2 cm ulcer with a clean base and raised, indurated margins (picture 4). The ulcer is generally painless and may be associated with regional lymphadenopathy. Direct visualization of spirochetes by darkfield microscopy or direct immunofluorescence, if available, is diagnostic of primary syphilis. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Clinical manifestations'.)

Complex aphthosis – Complex aphthosis is a term that describes patients with recurrent oral and genital aphthae in the absence of other clinical features of Behçet syndrome [34,35]. Complex aphthosis may be idiopathic or may occur in association with systemic disease, most often inflammatory bowel disease, HIV infection, and cyclic neutropenia. (See "Cyclic neutropenia".)

Behçet syndrome – Behçet syndrome is a rare, multisystem, inflammatory disease of unknown etiology characterized by painful genital and oral ulceration and uveitis. The genital ulcers are deep, painful, and heal with scarring (picture 5). (See "Clinical manifestations and diagnosis of Behçet syndrome".)

Crohn's disease – "Knife cut" ulcers are the most characteristic lesions and, if present, are practically pathognomonic for Crohn's disease (picture 6). They are usually located in the inguinal and interlabial folds and may predate the involvement of the gastrointestinal tract. (See "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents".)

Pyoderma gangrenosum – Pyoderma gangrenosum may rarely involve the vulva. Lesions begin as tender, inflammatory papules or pustules and rapidly evolve to a purulent ulcer with undermined borders. Histology shows abscess formation, intense infiltrate of neutrophils, areas of tissue necrosis, and vascular changes suggestive of leukocytoclastic vasculitis. (See "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis".)

Childhood vulval pemphigoid – Localized vulval pemphigoid of childhood is an exceedingly rare autoimmune bullous disease characterized by chronic, relapsing vulvar erosions [36-39]. A skin biopsy from perilesional tissue for direct immunofluorescence can confirm the diagnosis. (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Clinical features of mucous membrane pemphigoid'.)

TREATMENT

Overview — Because acute genital ulceration heals spontaneously, treatment is primarily supportive and includes reassurance, local hygiene and wound care, and pain control [4,40]. Patients and parents/caregivers should be reassured that ulcers are not infectious or sexually transmitted and that recurrence is infrequent.

Sitz baths with plain warm water may be used for gentle cleansing and debridement of ulcers. A handheld shower or spray bottle may also be used.

Topical anesthetics, such as lidocaine 2% viscous solution or 5% ointment, can be used as needed for temporary pain relief. Since external dysuria may be severe, the use of topical anesthetics before micturition may be helpful.

Oral analgesics, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and narcotics, may be given for pain that is not controlled with topical anesthetics. Patients with severe pain and secondary urinary retention may require hospitalization for catheter bladder drainage and parenteral analgesia [41].

Topical or systemic corticosteroids may be helpful in reducing inflammation and pain [4,32,41,42].

Approach — Our approach to the management of acute genital ulceration is as follows:

In patients with small, superficial ulceration and mild pain, topical anesthetics and oral analgesics usually provide adequate pain control. Lidocaine 2% viscous solution or jelly or 5% ointment can be applied locally multiple times per day.

For patients with superficial ulcerations and moderate pain, we suggest superpotent topical corticosteroids (group 1, (table 1)) in addition to topical and oral analgesics. Clobetasol propionate 0.05% ointment or fluocinonide 0.1% ointment may be applied two times per day until improvement.

Patients with multiple deep, necrotic ulcers and patients with intense pain that is not controlled by topical anesthetics and oral analgesics may benefit from a short course of oral corticosteroids. Prednisone at the dose of 0.5 to 1 mg/kg per day may be given for 7 to 10 days and then tapered over the following two weeks.

Patients with suspected bacterial superinfection or vulvar cellulitis should be treated with systemic antibiotics. Empiric antibiotic therapy should include methicillin-resistant Staphylococcus aureus (MRSA) coverage if MRSA is suspected based upon local epidemiology. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections".)

Although topical and systemic corticosteroids are commonly used in clinical practice for the treatment of acute genital ulceration, their efficacy in reducing pain and hastening healing has not been evaluated in clinical trials. Their use is based upon limited evidence from small case series and indirect evidence from studies on oral aphthous ulcers [4,32,41-44].

PROGNOSIS — Healing of acute genital ulceration typically occurs in two to six weeks, usually without scarring. In most patients, and particularly in those with acute genital ulceration associated with a viral infection or systemic illness, the disease does not recur. Recurrences have been reported in approximately 30 to 50 percent of the cases [2,9,41,45,46].

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

Definition and epidemiology – Acute genital ulceration, also known as "Lipschütz ulcer" or "ulcus vulvae acutum," is an uncommon condition characterized by self-limited ulcerations of the vulva or lower vagina. It occurs in nonsexually active adolescent females or young females, with over 90 percent of cases occurring in patients younger than 20 years. (See 'Introduction' above and 'Epidemiology' above.)

Clinical presentation – Ulcers are usually large (>1 cm) and deep, with a red-violaceous border and a necrotic base covered with a grayish exudate or an adherent gray-black eschar (picture 1). A partially symmetrical appearance ("kissing pattern") is characteristic (picture 2). Ulcers are usually preceded by influenza-like or mononucleosis-like symptoms. (See 'Clinical manifestations' above.)

Diagnosis – Acute genital ulceration is a clinical diagnosis and one of exclusion, based upon detailed history and complete physical examination. Proposed criteria for diagnosis include age <20 years; presence of one or multiple vulvar ulcerations; bilateral, "kissing" pattern; absence of sexual contact; absence of immunodeficiency; exclusion of other known causes of genital ulceration; and acute course with abrupt onset and spontaneous healing within six weeks. (See 'Diagnosis' above.)

Treatment – Treatment of acute genital ulceration is primarily supportive and includes wound care and relief of pain. In patients with small, superficial ulceration and mild pain, topical anesthetics usually provide adequate pain control. For patients with large, superficial ulcerations and moderate to severe pain, we suggest superpotent topical corticosteroids (group 1, (table 1)) in addition to topical anesthetics and oral analgesics (Grade 2C). Patients with multiple deep, necrotic ulcerations and patients with intense pain that is not controlled by topical anesthetics and oral analgesics may benefit from a short course of systemic corticosteroids. (See 'Treatment' above.)

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