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

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-examination revealed several small ulcer-like lesions on the vulva. Five days before the onset of genital ulcers, the patient was diagnosed with severe acute respiratory coronavirus 2 (SARS-CoV-2) via polymerase chain reaction. Symptoms of fatigue, nausea, headaches, and fever of 38.3°C were experienced on days 1–3 of her SARS-CoV-2 infection with persistent headache.

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 she described it as “normal.” She received all recommended immunizations except human papillomavirus, influenza, and SARS-CoV-2. Her psychosocial history was positive for anxiety, and school avoidance was diagnosed 6 months prior. She had recently been reluctant to attend school and attempted to come home several times a week because of anxiety related to contracting COVID-19.

The patient lived with her mother, father, and three older siblings. She was a sophomore in high school with a 3.8/4.0-grade point average and planned to attend college.

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

Vital signs were appropriate for her age, with no fever and a body mass index of 24.3. Her skin was without rashes, and there were no lesions on her 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 and nontender, 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 to 2.5 mm, and the affected labia were swollen and tender to the touch.

Differential diagnoses for genital ulcers include sexually transmitted infections (herpes simplex virus [HSV], HIV infection, syphilis) and noninfectious diseases that cause genital ulcerations (Behcet's syndrome, Crohn's disease, complex aphthosis, pyoderma gangrenosum, and childhood vulval pemphigoid; ). Numerous case reports have described genital ulcers following infections, including cytomegalovirus, influenza, mumps virus, salmonella, mycoplasma, and Epstein-Barr virus (). 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. developed an algorithm for evaluating and treating acute genital ulcers following the exclusion of HSV (Figure 1).

Initial testing included a complete blood count with differential and HSV polymerase chain reaction. Shared decision-making was used with the patient and her mother to determine additional testing. They agreed to Epstein-Barr virus titers, cytomegalovirus titers, and a polymerase chain reaction 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 (LUs), also known as aphthous ulcers, acute genital ulcers, and acquired genital ulcerations, are rare, painful vulvar and vaginal ulcers that occur in nonsexually active adolescent females (). First identified in 1913 by Australian dermatologist Benjamin Lipshutz, this uncommon condition is described by the sudden onset of vulvar ulcers in nonsexually active females with systemic signs of infection (). These ulcers typically present with a prodromal phase of viral symptoms, including fever, fatigue, and malaise, followed by 0.1 to 2.5 cm single or multiple vulvar ulcerations (). 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 microthrombi that eventually lead to painful necrotizing ulcers (). LUs are 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 (; ). Evidence suggests that LUs may be a precursor to certain autoimmune conditions (). Regularly scheduled health supervision visits are encouraged to optimize early diagnosis and treatment of 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 vaccination (; ). The most common cause of genital ulcers in young, sexually active females is either genital herpes or syphilis. LUs are a diagnosis of exclusion, so it is important to rule out other causes of genital ulcers before making the diagnosis. Conversely, it is important to consider the diagnosis of LUs in sexually inactive females to avoid misdiagnosis and emotional distress.

Genital herpes, caused by 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 initial herpes infection is 4 days (ranging from 2 to 12) after exposure. The vesicles open, leaving painful ulcers that take 2–4 weeks to heal. Systemic symptoms of an initial herpes outbreak can include fever, body aches, swollen lymph nodes, and headache (). 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 enters the body; in women, this is usually around the vagina or rectum. These sores are normally firm, round, and painless, lasting 3–6 weeks regardless of treatment ().

The mother and patient were advised that LUs is a clinical diagnosis of exclusion, and other causes must be ruled out before a definitive diagnosis can be made (). 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 because of dysuria. She was advised to sit in a shallow bath and urinate at the end if she was reluctant to void because of discomfort. Further comfort care included avoiding perfumed soaps and lotions and wearing restrictive clothing. The patient was reassured that LUs are self-limiting and the treatment is supportive care.

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 1 week to inform them that all test results were negative and in 2 weeks to check on the patient's symptoms. At that time, the patient was symptom-free, and the vaginal lesions had resolved.

SARS-CoV-2 infections have been associated with numerous local and systemic reactions. To date, case reports have highlighted the development of LUs following SARS-CoV-2 vaccination and infection (; ; ). This case report described the development of LUs in an unvaccinated female with a recent SARS-CoV-2 infection. Adding LUs to the list of differential diagnoses in nonsexually 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 vaccinated against SARS-CoV-2 and those with a recent SARS-CoV-2 infection.