Generalized Vaccinia; This case was obtained from a scientific literature on date 03SEP2019.  A 19-year-old-male patient developed generalized vaccinia (GV) (PT: Generalised vaccinia) and Epstein Barr Virus Infection/ mononucleosis (PT: Infectious mononucleosis), following the administration of ACAM2000 (smallpox (vaccinia) vaccine, live)   Case report: A 19-year-old presented to his aid station with concern for a spreading vesicular rash 9 days after a primary inoculation with the smallpox vaccine. The rash was limited to the inoculation site on his left shoulder. He had no medical history of eczema, atopic dermatitis, or other rashes and reported no systemic symptoms. His vitals also were within normal limits. A clinical diagnosis of inadvertent inoculation (also termed accidental infection) with satellite lesions was made, and he was discharged with counseling on wound care and close follow-up. Two days later, on post vaccination day 11, he presented with new symptoms of a headache, fever, chills, diffuse myalgia, sore throat, and spreading erythematous macules, papules, and vesicles on his arms, chest, abdomen, back, legs, and face. His vital signs were remarkable for tachycardia with heart rate of 100 bpm and a fever of 103 degree Fahrenheit (39.4 degree Celsius). He was sent to the emergency department with a presumed generalized GV diagnosis.   A complete blood count, liver function tests, and basic metabolic panel were unremarkable. Given his symptom of pharyngitis, a rapid strep test was performed. The test was negative, and a throat culture showed no growth. A mononucleosis screen also was performed and was positive. The patient was diagnosed with mononucleosis and GV. His condition improved, and his vital signs stabilized with conservative treatment without the need for vaccine immune globulin (VIG). He convalesced for 72 hours and was referred to dermatology on the following day. He was quarantined in a single occupancy barracks room until all lesions crusted over to address the concern for spread of the virus to non-immunized coworkers or family members.   On post vaccination day 12, the patient continued to be clinically well, and he remained afebrile. The dermatologist obtained a skin biopsy from a lesion on the patient's right shin. The biopsy demonstrated marked epidermal necrosis with peripheral keratinocytes showing ballooning degeneration and viral cytopathic changes consistent with GV. Antibody titers showing high levels of Epstein-Barr virus (EBV) capsid IgM and IgG present confirmed mononucleosis infection within the past 6 months. The patient remained clinically well and was released from quarantine on post vaccination day 22 when all lesions crusted over.  Author's comment: The smallpox vaccination is unique among vaccinations. It is the only vaccine that is administered via inoculation with a bifurcated needle, requires regular follow-up care, and can be spread to casual contacts. It is important for any practitioner administering the smallpox vaccine to be aware of associated AEs. A greater knowledge of the unique challenges with the smallpox vaccine allows for better patient selection that eliminates those with conditions that impair their immune system and improves patient education.  Company' comment:The Company considers that the generalized vaccinia (GV) was probably related to the ACAM vaccination. Such widespread skin reaction to vaccine occurs due to virus dissemination beyond the initial inoculation site of small pox vaccine throughout systemic transmission. Mononucleosis is considered concurrent condition and present symptoms were probably due to a relapse or worsened due to the GV. Because the tests showed an onset of about six months, mononucleosis a concurrent infection and not considered as an adverse event. Symptoms are not coded as per MedDRA point to consider. The case met the criterion of medically significant.; Sender's Comments: The Company considers that the generalized vaccinia (GV) was probably related to the ACAM vaccination. Such widespread skin reaction to vaccine occurs due to virus dissemination beyond the initial inoculation site of small pox vaccine throughout systemic transmission. Mononucleosis is considered concurrent condition and present symptoms were probably due to a relapse or worsened due to the GV. Because the tests showed an onset of about six months, mononucleosis a concurrent infection and not considered as an adverse event. Symptoms are not coded as per MedDRA point to consider. The case met the criterion of medically significant.