Lipschutz Ulcers in an Adolescent After Sars-CoV-2 Infection.

This case report describes a 15-year-old female who presented with acute onset of painful genital ulcers. She denied being sexually active and tested positive for severe acute respiratory coronavirus 2 five days prior. Associated symptoms on days 1 to 3 included fatigue, nausea, headaches, and fever. Lipschutz ulcers (LUs), also known as aphthous ulcers, acute genital ulcers, and acquired genital ulcerations; are an uncommon, self-limiting, nonsexually transmitted condition characterized by the rapid onset of painful, necrotic ulcerations of the vulva or lower vagina. The pathogenesis of LUs is unclear, and the diagnosis is one of exclusion.

Chief Complaint and History of Present Illness

A 15-year-old Caucasian female presented to her pediatric primary care office accompanied by her mother with a chief complaint of painful vaginal sores and a headache. The symptoms began 2 days prior with vaginal itching and burning with urination. Her pain score was 5/10 at baseline and 8/10 with urination. She noted a small amount of thin white vaginal discharge. Self-exam revealed several small ulcer-like lesions on the vulva. Five days prior to the onset of genital ulcers, the patient was diagnosed with SARS-CoV-2 via polymerase chain reaction (PCR). Symptoms of fatigue, nausea, headaches, and fever of 38.3°Celsius were experienced on days 1 through 3 of her SARS-CoV-2 infection with persistent headache.

Medical History

The patient was a healthy and developmentally appropriate 15-year-old female with no significant past medical history. She had no chronic medical conditions and no previous hospitalizations or surgeries. She had no known allergies and did not take any prescription, over-the-counter, or herbal medications. She identified as a heterosexual female and denied current or past sexual activity, sexual abuse, and sexually transmitted infections. Her last menstrual cycle was 3 weeks ago and described as “normal.” She had received all recommended immunizations except for human papilloma virus, influenza, and SARS-CoV-2.

Her psychosocial history was positive for anxiety and school avoidance diagnosed 6 months prior. She had recently been reluctant to attend school and attempted to come home several times a week due to anxiety related to contracting COVID-19.

Social and Developmental History

The patient lived with her mother, father, and three older siblings. She was a sophomore in high school with a 3.8/4 grade point average and plans to attend college.

Review or Systems

Constitutional symptoms included an alert, developmentally appropriate 15-year-old female who was tearful and anxious. She reported vaginal sores, headache, and fatigue. She denied urinary frequency, urgency, abdominal or flank pain, as well as vaginal odor. She stated she was tearful and anxious due to physical and emotional distress caused by the genital ulcers.

Physical Examination

Vital signs were appropriate for age with no fever and she had a BMI of 24.3. Her skin was without rashes; and there were no lesions on hands or feet. She had clear postnasal drainage with hypertrophic bilateral erythematous nasal turbinates. Her lung sounds were clear to auscultation bilaterally. No cervical or inguinal lymphadenopathy was appreciated. Her heart rate was regular, normal S1 and S2, with no murmurs. Her abdomen was soft, non-tender with active bowel sounds in all quadrants without hepatosplenomegaly or costal vertebral tenderness. She was Tanner Stage V with five painful erosive ulcer-like lesions on the labia minora with a scant amount of thin white vaginal discharge. The lesions ranged from 1.5-2.5 mm and the affected labia was swollen and tender to touch.

Differential Diagnoses

Differential diagnoses for genital ulcers include sexually transmitted infections (herpes simplex virus [HSV], HIV infection, syphilis) and non-infectious diseases that cause genital ulcerations (Behcet's syndrome, Crohn's disease, complex aphthosis, pyoderma gangrenosum, and childhood vulval pemphigoid) (Moise et al., 2018). Numerous case reports have described genital ulcers following infections including cytomegalovirus (CMV), influenza, mumps virus, salmonella, mycoplasma and Epstein-Barr virus (EBV) (Wojcicki et al., 2022). Because she was not sexually active and was recently diagnosed with SARS-CoV-2 having symptoms of fatigue, nausea, headaches, and fever; a viral etiology was presumed. Rosman et al. (2012) and colleagues developed an algorithm for evaluation and treatment of acute genital ulcers following exclusion of HSV (Figure 1 ).

Figure 1

Algorithm for Evaluation and Management of AGU in non-sexually active young girls (Rosman et al., 2012) AGU = Acute Genital Ulcers, HSV = Herpes Simplex Virus, PCR = Polymerase chain reaction, GI = gastrointestinal, EBV = Epstein-Barr Virus, CMV = Cytomegalovirus

Diagnostic Studies

Initial testing included a complete blood count with differential and HSV PCR. Shared decision-making was used with the patient and her mother to determine additional testing. They agreed to EBV titers, CMV titers, and a PCR test for influenza A and B. She also agreed to additional testing and a referral to gynecology or dermatology if the ulcers did not significantly improve in 2 weeks or if the ulcers reoccurred.

Lipschutz Ulcers

Lipshutz ulcers (LU), also known as aphthous ulcers, acute genital ulcers, and acquired genital ulcerations are rare, painful vulvar and or vaginal ulcerations that occur in non-sexually active adolescent females (Polito & Morley, 2022). First identified in 1913 by Australian dermatologist Benjamin Lipshutz, this uncommon condition is described by sudden onset of vulvar ulcers in non-sexually active females with systemic signs of infection (Christl et al., 2021). These ulcers typically present with a prodromal phase of viral symptoms including fever, fatigue, and malaise followed by 1 mm to 2.5 cm single or multiple vulvar ulcerations (Pereira et al., 2021). The pathogenesis of LU is thought to be a hypersensitivity immune response to a viral or bacterial illness that results in the formation of immune complexes in the dermal vessels causing micro-thrombi that eventually lead to painful necrotizing ulcers (Moise, 2018). Lipschutz ulcers is a self-limiting condition, with spontaneous healing typically in 2-6 weeks. Treatment is focused on supportive care including managing pain, mitigating secondary infection, and providing patient reassurance and anticipatory guidance (Wojcicki & O”Brien, 2021; Wyles et al., 2017). There is evidence to suggest that LU may be a precursor to certain autoimmune conditions (Polito & Morley, 2022). Regularly scheduled health supervision visits are encouraged to optimize early diagnosis and treatment of any new disease processes.

Acute genital ulcers have been reported following Epstein-Barr virus, cytomegalovirus, influenza A and B, adenovirus, Mycoplasma pneumonia, and now SARS-CoV-2 infection and SARS-CoV-2 vaccination (Hsu et al., 2022; Wojcicki et al., 2021). The most common cause of genital ulcers in young sexually active females is either genital herpes or syphilis. Lipschutz ulcers are a diagnosis of exclusion, so it is important to rule out other causes of genital ulcers prior to making the diagnosis. Conversely, it is important to consider the diagnosis of LU in sexually inactive females, to avoid misdiagnosis and emotional distress.

Genital Ulcers in Sexually Transmitted Infections

Genital herpes, caused by the HSV, is a common sexually transmitted infection that is more common in women than men. Herpes lesions typically appear as one or more vesicles on or around the genitals or rectum. The average incubation period for an initial herpes infection is 4 days (ranging from 2 to 12) after exposure. The vesicles open, leaving painful ulcers that take two to four weeks to heal. Systemic symptoms with an initial herpes outbreak can include fever, body aches, swollen lymph nodes and headache (Centers for Disease Control and Prevention [CDC], 2021). Syphilis is a sexually transmitted infection that develops in stages (primary, secondary, latent, and tertiary) and each stage has different symptoms. During the primary stage of syphilis, single or multiple lesions develop where syphilis entered the body, in women this is usually around the vagina or rectum. These sores are normally firm, round, and painless, lasting 3 to 6 weeks regardless of treatment (CDC, 2022).

Evidence Based Management

The mother and patient were advised that LU is a clinical diagnosis of exclusion and other causes needed to be ruled out before a definitive diagnosis could be made (Moise et al., 2018). Comfort measures were discussed including alternating acetaminophen and ibuprofen. Additional self-care included the application of cold compresses to the affected genital areas. The patient was instructed to remain well hydrated and to avoid urine retention due to dysuria. She was advised to sit in a shallow bath and urinate at the end if she was reluctant to void due to discomfort. Further comfort care included the avoidance of perfumed soaps, lotions, and wearing restrictive clothing. The patient was reassured that LU are self-limiting and the treatment is supportive care.

Follow-Up

The patient was discharged home and informed that they would be contacted with the test results. Follow up phone calls were made to the family in one week to inform them that all test results were negative, and in two weeks to check on the patient's symptoms. At that time, the patient was symptom free and the vaginal lesions had resolved.

Case Summary

SARS-CoV-2 infections have been associated with numerous local and systemic reactions. To date, case reports have highlighted the development of LU following SARS-CoV-2 vaccination and infection (Christl et al., 2021; Hsu et al., 2022; Wojcicki & O'Brien, 2021). This case report described the development of LU in an unvaccinated female with a recent SARS-CoV-2 infection. Adding LU to the list of differential diagnoses in non-sexually active females with genital ulcers will aid in not missing this uncommon diagnosis. Further research is needed to determine the causal relationship between the development of LU in adolescent females recently vaccinated against SARS-CoV-2 and those with a recent SARS-CoV-2 infection.

Declaration of Competing Interest

We, the co-authors, of this manuscript made significant contributions to the conception, design, execution, and interpretation of this case report. We ascertain that this is an original work and that we have appropriately referenced work of other authors throughout the manuscript. This manuscript has not been submitted for publication to any other journal. We do not have any conflicts of interest associated with this manuscript and there has been no financial support for this work that could influence its outcome.