Aphthous ulcer of the vagina, fever, fatigue, myalgias and sores in vaginal area; This is a spontaneous report based on unpublished manuscript from a contactable physician.   A 16-year-old non-sexually active female presented to the pediatric gynecology clinic with vaginal pain. Six days prior she had received her second dose of the Pfizer BioNTech (BNT162b2) COVID-19 vaccine. Within 24 hours of receiving the vaccine, she developed fever, fatigue, myalgias and sores in her vaginal area. Over the next 2 days, right sided lesions in her vaginal area coalesced and became more painful. She presented to urgent care with a fever of 105 degrees Fahrenheit where she was diagnosed with a Bartholin gland abscess and prescribed amoxicillin-clavulanate. Despite antibiotic therapy, her symptoms continued to worsen prompting her to return to clinic two days later. By this point, the lesions were covered in exudate with a necrotic, ring-like border. Gynecology was consulted and recommended assessment for likely Lipschutz ulcers. In gynecology clinic, the patient's lesions were exquisitely painful, resulting in difficulty with urination, defecation, and walking. She had no respiratory symptoms and no known COVID-19 exposures. Her medical history was significant for several congenital conditions requiring corrective surgeries including soft palate cleft, club foot, syndactyly of her left foot and congenital hearing impairment in the right ear. Additionally, the patient reported a history of recurrent oral ulcerations, but no previous history of genital ulcerations. Her family history was notable for severe canker sores in her father and uncle requiring medical intervention and hospitalization. The patient denied any history of sexual activity. On exam, the patient was afebrile and in no acute distress. Her genitourinary exam was significant for an ulcerated lesion with adherent yellow and grey fibrinous exudate on the right labia minora measuring 3 cm x 2 cm. The ulcer was well-demarcated with a necrotic appearing border. Desquamation was observed of the surrounding tissue and the posterior fourchette. The affected right labia was markedly swollen in comparison to the left. Laboratory evaluation was negative for SARS-COV-2 RNA by anterior nares swab. Viral polymerase chain reaction testing of the vulvar lesion was negative for herpes simplex virus (HSV) 1 and 2 as well as serum testing for HSV 1 and 2 antibodies. Epstein Barr nuclear antigen (EBNA) antibodies were present, indicating prior infection with EBV. Testing for CMV, syphilis (RPR), and human immunodeficiency virus (HIV) were negative. Fluorescent antinuclear antibody screen was negative. Clinical history and genital examination findings were consistent with vulvar aphthous ulcers in association with influenza-like symptoms following Pfizer BioNTech (BNT162b2) COVID-19 vaccination. The patient was prescribed topical clobetasol 0.05% ointment and instructed to apply to the affected area twice daily for 14 days. Her pain management regimen included ibuprofen and acetaminophen as needed, as well as topical lidocaine gel. She was started on norethindrone 5 mg orally daily for menstrual suppression while her ulcerations were healing. She presented for follow up two weeks later and reported improvement in her symptoms, although she was experiencing sensitivity with vulvar manipulation and pain with urination. The ulcerated lesion was noted to be resolving along the medial aspect of the right vaginal introitus. Vulvar edema had resolved. She reported the appearance of an oral ulcer several days prior and physical exam was consistent with aphthous ulcer on the inner aspect of her lower lip. Patient was referred to rheumatology in light of her recurrent oral aphthous ulcers, vulvar ulcer and family history of oral ulcerations. The case was submitted to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS) due to the temporal relationship with COVID vaccine administration.  Summary and Conclusions This is the first case report to describe a potential relationship between the development of vulvar aphthous ulcers and COVID-19 vaccination. Our patient had typical clinical features of aphthous ulcer including an influenza-like prodrome and characteristic dermatologic manifestations which occurred after receiving the Pfizer COVID vaccine.  The temporal relationship of our patient's symptoms to Pfizer BioNTech (BNT162b2) vaccination in the context of a negative test for SARS-COV-RNA, as well as other infectious etiologies, suggest that her systemic symptoms and vulvar aphthous ulcer may have occurred secondary to an immune response precipitated by the vaccine. However, there are several other factors in this patient, including evidence of past infection with EBV and medical and family history of recurrent oral ulcers, which potentially contributed to their presentation.  This case suggests that vulvar aphthous ulcers may be precipitated by vaccination, however, further research is required to establish a causal relationship. One proposed mechanism for study is to investigate how the immune system's response to vaccination recapitulates the pro-inflammatory response associated with vulvar aphthous ulcers secondary to viral illness.  Event occurred in a country different from that of the reporter.  This may be a duplicate if the reporter also submitted directly to his/her local agency.  Follow-up attempts are completed. No further information is expected.; Sender's Comments: Based on the description given in the narrative, there is reasonable possibility of causal association between the Serious event  Aphthous Ulcer and the suspect BNT162B2 cannot be excluded. The impact of this report on the benefit/risk profile of the Pfizer drug is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate.