Sex: M
Vaccine: SMALL
Symptoms: Pneumonitis, Polymerase chain reaction positive, Skin lesion, Sudden death, Toxicologic test normal
Clinical narrative: Necrotizing eosinophilic myocarditis; Mild concentric left ventricular hypertrophy; Allergic rhinitis; Sudden death; Cardiomegaly; SERIOUSNESS CRITERIA: OTHER - MEDICALLY SIGNIFICANT  This case was received on 16 June 2014 via a third party query tool search on the VAERS database, under reference number 526687.  A 24-year-old male patient had received a SMALLPOX (VACCINIA) LIVE VACCINE (ACAM2000, lot number not reported) on 07 March 2014.  On 19 March 2014, 12 days following vaccination, the patient experienced sudden death and cardiomegaly with four chamber dilation.  The patient histologic diagnosis was myocarditis.  At the time of this report toxicology is still pending.  The patient's other medications, current illnesses and history were reported as none. No further information was available at the time of the report.  Although the smallpox vaccine manufacturer was reported as unknown in this case, ACAM2000 was the only licensed smallpox vaccine at the time of the patient's vaccination.  The patient outcome was fatal.  Follow-up information for this unsolicited report was received from a healthcare professional on 08 December 2014, and included a redacted copy of the autopsy report.  The patient was found unresponsive in his quarters.  Cause of death was necrotizing eosinophilic myocarditis, and manner of death was natural.  A cardiovascular pathology consultation showed predominant interstitial inflammation, a mixed inflammatory infiltrate of macrophages, neutrophils, eosinophils and lymphocytes, and patchy myocyte necrosis.  The impression from the consultation was necrotizing eosinophilic myocarditis with mild concentric left ventricular hypertrophy.    A lesion on the left shoulder was consistent with recent smallpox vaccination, and recent smallpox vaccination was confirmed by serology.  No ethanol was detected in the blood or vitreous fluid.  Acetaminophen and diphenhydramine were detected.  The opinion of the examiner was that the patient died of necrotizing eosinophilic myocarditis, temporally related with administration of a smallpox vaccination.  Cause and effect relationship between smallpox vaccination and death could not be definitively established or ruled out.  Follow-up information for this unsolicited report was received from a healthcare professional on 11 December 2014 and included an updated redacted copy of the autopsy report.  Diagnostic comments included orthopox was negative by PCR - fresh frozen and tissue extracts from the paraffin blocks.  Specimen identification final comment: The assay used to detect the presence of human DNA in the sample provided has been changed from beta actin to RNASEP. A tissue culture was not done.  Orthopox IgG was negative. Orthopox and ELISA IgM was positive.  The histologic features are predominant interstitial inflammation, a mixed inflammatory infiltrate of macrophages, neutrophiles, eosinophils and lymphocytes and patchy myocyte necrosis.  This pattern is that of an aggressive form of hypersensitivity (allergic) myocarditis with myocyte necrosis that has been most frequently associated with a reaction to drugs, especially antibiotics.    The following is verbatim from the report: "In this case, the myocarditis seems mostly likely the cause of death.  It is impossible to establish a causative link between the myocarditis and the vaccination.  However, if there was no other exposure to drugs (especially antibiotics) in this case within the last few weeks to months, then a vaccinia-related myocarditis seems most likely."  Documents held by sender:  Redacted Autopsy report.  Follow-up information derived from a full-text article, was received on 19MAY2023.  It described a 24-year-old male patient who had "allergic rhinitis" (PT: Rhinitis allergic), developed "necrotizing eosinophilic myocarditis" (PT: Eosinophilic myocarditis), "mild concentric left ventricular hypertrophy" (PT: Ventricular hypertrophy) and had "sudden death" (PT: Sudden death) following the immunisation with ACAM2000 (smallpox vaccine, live).  Case report: The report describes a 24-year-old male patient with good baseline health (prior to immunization), meeting physical fitness standards, and without any diagnoses that impacted the ability to work or receive the smallpox vaccine (SPV). Coronary artery disease or cardiomyopathy was not present in the patient. Reportedly, the patient concomitantly received typhoid Vi (Typhoid vaccine) and human papillomavirus (HPV) vaccine along with smallpox vaccine. Furthermore, the patient did not seek care post vaccination and developed allergic rhinitis for which he received antihistamines (unspecified).  The patient underwent certain laboratory investigations which included negative viral polymerase chain reaction (PCR) studies (including vaccinia of the heart tissue) and negative toxicology studies.  Additionally, it was reported that the patient was hospitalised (reason unknown), and no arrhythmia was documented. Following 12 days of vaccination, the patient suddenly died. The histology at autopsy confirmed necrotizing eosinophilic myocarditis and mild concentric hypertrophy. The cause of death was reported as hypersensitivity eosinophilic myocarditis.  Author's comment:  This was very rare case with having a sudden death associated with classic hypersensitivity myocarditis histology. The challenge of causality assessments for complex, prolonged illness following acute presentation before death often involves divergent opinions depending on specialty perspectives within a multidisciplinary review.  Based on the above available information in the source document, two individual case safety reports (14000046SP and 12AV00003RG) were created and linked in the database.  Company comment: A 24-year-old male patient received ACAM2000 on 07 March 2014. Following the vaccination, the patient developed allergic rhinitis, for which he received unspecified antihistamines. Patient was hospitalized on 19 March 2014 for unknown reasons. 12 days following vaccination, the patient suddenly died.  No prior medical history, toxicology reports, or concomitant medications were reported.  The histology at autopsy confirmed necrotizing eosinophilic myocarditis and mild concentric left ventricular hypertrophy. The cause of death was reported as hypersensitivity eosinophilic myocarditis. Eosinophilic myocarditis is a rare subtype of myocarditis, recognized by severe heart failure and marked eosinophilia infiltration which is rare and often fatal.  Cardiology pathology reports revealed interstitial inflammation and myocyte necrosis, supporting the diagnosis in the autopsy report.  Although myocarditis is a listed event for ACAM2000, eosinophilic myocarditis is not listed.  Based upon the absence of other known etiologies, and no reported implication to other vaccines, the role of ACAM2000 cannot be ruled out and the causality of rhinitis allergic, eosinophilic myocarditis, ventricular hypertrophy, and sudden death is assessed as possible. The case is considered serious as per medical assessment.; Sender's Comments: A 24-year-old male patient received ACAM2000 on 07 March 2014. Following the vaccination, the patient developed allergic rhinitis, for which he received unspecified antihistamines. Patient was hospitalized on 19 March 2014 for unknown reasons. 12 days following vaccination, the patient suddenly died.  No prior medical history, toxicology reports, or concomitant medications were reported.  The histology at autopsy confirmed necrotizing eosinophilic myocarditis and mild concentric left ventricular hypertrophy. The cause of death was reported as hypersensitivity eosinophilic myocarditis. Eosinophilic myocarditis is a rare subtype of myocarditis, recognized by severe heart failure and marked eosinophilia infiltration which is rare and often fatal.  Cardiology pathology reports revealed interstitial inflammation and myocyte necrosis, supporting the diagnosis in the autopsy report.  Although myocarditis is a listed event for ACAM2000, eosinophilic myocarditis is not listed.  Based upon the absence of other known etiologies, and no reported implication to other vaccines, the role of ACAM2000 cannot be ruled out and the causality of rhinitis allergic, eosinophilic myocarditis, ventricular hypertrophy, and sudden death is assessed as possible. The case is considered serious as per medical assessment.; Reported Cause(s) of Death: Necrotizing eosinophilic myocarditis