Vulvar Lipschütz Ulcer: Unveiling the Enigma of Etiology, Diagnosis, and Emerging Links with SARS-CoV-2

In clinical practice, the identification of the underlying cause of genital ulcers can be a challenging task for healthcare providers.

Genital ulcers can manifest as a result of various etiologies, ranging from infectious causes, especially sexually transmitted infections (STIs) such as Herpes simplex virus, to a spectrum of non-infectious conditions including autoimmune diseases, malignancies, inflammatory processes, and even trauma, including sexual abuse.

Among the myriad of causes, Lipschütz ulcer (LU), also known as “ulcus vulvae acutum” or “acute genital ulceration” stands out as a unique and intriguing clinical entity.

First described in 1913 by Benjamin Lipschütz, LU was initially considered rare, but recent studies have revealed its prevalence, accounting for up to 30% of vulvar ulcerations.

Lipschütz ulcer primarily affects young women, with an average age of 29.1 years, although cases have been reported in children and older women. The hallmark clinical presentation of LU is the sudden onset of painful ulcers that can appear anywhere on the vulva, seemingly without an identifiable cause.

These ulcers typically measure between 0.1 to 2.5 cm in diameter, characterized by a red border and a necrotic center covered by grey exudate or grey-black eschar. Patients may also experience labial edema, fever, lymphadenopathy, and occasionally present with non-gynecological symptoms. Notably, “kissing lesions” often occur bilaterally.

Etiology of Lipschütz Ulcer

The precise etiology of Lipschütz ulcer remains elusive. However, one prevailing theory suggests that it results from a hypersensitive immune response triggered by bacterial or viral infections. This immune response leads to the formation of immune complexes within dermal arteries, subsequently causing microthrombi and the development of painful necrotizing ulcers. Despite this hypothesis, the exact infectious agent responsible for LU remains unidentified.

Diagnostic Criteria for Lipschütz Ulcer

To diagnose Lipschütz ulcer, healthcare providers rely on a set of diagnostic criteria:

Major Criteria:

• Acute onset of at least one painful vulvar ulcer.
• Exclusion of infectious and non-infectious causes.

Minor Criteria:

• Localized ulcer at the level of the vestibule or labia minora.
• Abstention from sexual intercourse in the last 3 months or patient who has never had sexual intercourse.
• Flu-like symptoms.
• Development of a systemic infection at least 2–4 weeks preceding ulcer development.

Common infectious causes that must be excluded include Epstein–Barr Virus (EBV), Mycoplasma Pneumoniae, Cytomegalovirus (CMV), Toxoplasma gondii, Herpes Simplex Virus 1–2 (HSV 1–2), Influenza virus, Mumps virus, Salmonella, or Parvovirus B19 (PVB19). Non-infectious causes such as Behçet’s syndrome, Crohn’s disease, bullous diseases, cancer, and prior trauma should also be considered and ruled out.

Emerging Associations with SARS-CoV-2

In recent times, an intriguing association has emerged between Lipschütz ulcer and SARS-CoV-2, the virus responsible for COVID-19.

Several cases of Lipschütz ulcer development have been reported in conjunction with SARS-CoV-2 infection or following COVID-19 vaccination.

The COVID-19 pandemic has introduced a range of cutaneous manifestations, including those associated with SARS-CoV-2 infection and vaccination.

A hypothesis proposes that both SARS-CoV-2 infection and COVID-19 vaccination induce a robust inflammatory response.

This response may be consistent with the pathogenesis of Lipschütz ulcer, involving the formation of immune complexes, activation of the complement system, and subsequent inflammatory reactions leading to microthrombosis and tissue necrosis. Notably, histological examinations of Lipschütz ulcer biopsies associated with EBV infection have revealed localized immune complex vasculitis, supporting this proposed mechanism.

Management and Treatment

The primary goal in managing Lipschütz ulcer is to provide symptomatic relief. These ulcers are self-limiting and typically resolve spontaneously within 2 to 6 weeks. Therefore, therapy primarily focuses on pain control, prevention of secondary infections, patient reassurance, and guidance.

Local support measures often include the use of topical lidocaine 5% for pain relief, while oral non-steroidal anti-inflammatory drugs (NSAIDs) may be employed to address flu-like symptoms. In cases where localized control proves insufficient in managing intense pain, systemic treatment with oral corticosteroids may be considered, although they do not hasten ulcer remission.

Conclusion

Lipschütz ulcer presents a perplexing clinical challenge, often causing anxiety in affected patients due to its painful nature. Diagnosing Lipschütz ulcer necessitates a comprehensive clinical history, exclusion of infectious and non-infectious causes, serological screening, and culture tests.

In cases where all other potential causes are ruled out, healthcare providers should consider SARS-CoV-2 infection or previous COVID-19 vaccination as potential triggers.

This review highlights the need for further research to elucidate the etiopathogenesis, improve diagnostic criteria, and refine treatment strategies for Lipschütz ulcer. Prospective studies could provide more robust insights into this enigmatic condition, which, despite its painful presentation, typically follows a self-limiting course.

In conclusion, healthcare providers should be vigilant in considering Lipschütz ulcer in their differential diagnosis when faced with vulvar ulcers, while reassuring patients about the typically benign nature of the condition and offering effective supportive therapy.

reference link : https://www.mdpi.com/2079-9721/11/3/121