Myocarditis and pericarditis recovery following smallpox vaccine 2002-2016: A comparative observational cohort study in the military health system.

OBJECTIVES: (1) Characterize the initial clinical characteristics and long-term outcomes of smallpox vaccine-associated hypersensitivity myocarditis and pericarditis (MP) in United States service members. (2) Describe the process of case identification and adjudication using the 2003 CDC nationally defined myocarditis/pericarditis epidemiologic case definitions to include consideration of case-specific diversity and evolving evidence. BACKGROUND: Between 2002 and 2016, 2.546 million service members received a smallpox Vaccinia vaccine. Acute MP is associated with vaccinia, but the long-term outcomes have not been studied. METHODS: Records of vaccinia-associated MP reported to the Vaccine Adverse Event Reporting System by vaccination date were adjudicated using the 2003 MP epidemiologic case definitions for inclusion in a retrospective observational cohort study. Descriptive statistics of clinical characteristics, presentation, cardiac complications, and time course of clinical and cardiac recovery were calculated with comparisons by gender, diagnosis and time to recovery. RESULTS: Out of over 5000 adverse event reports, 348 MP cases who survived the acute illness, including 276 myocarditis (99.6% probable/confirmed) and 72 pericarditis (29.2% probable/confirmed), were adjudicated for inclusion in the long-term follow-up. Demographics included a median age of 24 years (IQR 21,30) and male predominance (96%). Compared to background military population, the myocarditis and pericarditis cohort had a higher percentage of white males by 8.2% (95% CI: 5.6, 10.0) and age <40 years by 4.2% (95% CI: 1.7,5.8). Long-term follow-up documented full recovery in 267/306 (87.3%) with 74.9% recovered in less than a year (median ~3 months). Among patients with myocarditis, the percentage who had a delayed time to recovery at time of last follow-up was 12.8% (95% CI: 2.1,24.7) higher in those with an acute left ventricular ejection fraction (EF) of ≤50% and 13.5% (95% CI: 2.4,25.7) higher in those with hypokinesis. Patient complications included 6 ventricular arrhythmias (2 received implanted defibrillators) and 14 with atrial arrhythmias (2 received radiofrequency ablation). Three of 6 patients (50%) diagnosed with cardiomyopathy had clinical recovery at their last follow-up date. CONCLUSIONS: Hypersensitivity myocarditis/pericarditis following the smallpox vaccine is associated with full clinical and functional ventricular recovery in over 87% of cases (74.9% <1 year). A minority of MP cases experienced prolonged or incomplete recovery beyond 1 year.

Heterologous effect of influenza vaccination on molluscum contagiosum infection; a case report of siblings.

BACKGROUND: Molluscum contagiosum virus (MCV) is a benign, common cutaneous infection predominantly affecting the younger pediatric population. Traditional treatments may be time consuming with variable efficacy. Time to spontaneous resolution is variable and treatment is often sought to shorten duration of infection, prevent further autoinoculation, prevent infectious spread to others and treat cosmetic intolerability. CASE PRESENTATION: We present the case of two patients with complete, simultaneous clearance of their molluscum contagiosum infections after receiving a routine 2018 quadrivalent influenza vaccination. Neither patient has had recurrence of molluscum contagiosum or permanent scarring. We review trials of intralesional immunotherapy in treatment of cutaneous infections to theorize the mechanism of MCV infection clearance post influenza vaccination. CONCLUSION: We propose a delayed-type hypersensitivity reaction was induced as a heterologous effect of the influenza vaccination, similar to that seen in current immunotherapy treatments. This is the first reported case of MCV-directed immune reaction with infection clearance after influenza vaccination.

Myopericarditis Associated With Smallpox Vaccination Among US Army Personnel - Fort Hood, Texas, 2018.

OBJECTIVE: In March 2018, the US Department of Defense (DOD) added the smallpox vaccination, using ACAM2000, to its routine immunizations, increasing the number of persons receiving the vaccine. The following month, Fort Hood reported a cluster of 5 myopericarditis cases. The Centers for Disease Control and Prevention and the DOD launched an investigation. METHODS: The investigation consisted of a review of medical records, establishment of case definitions, causality assessment, patient interviews, and active surveillance. A 2-sided exact rate ratio test was used to compare myopericarditis incidence rates. RESULTS: This investigation identified 4 cases of probable myopericarditis and 1 case of suspected myopericarditis. No alternative etiology was identified as a cause. No additional cases were identified. There was no statistically significant difference in incidence rates between the observed cluster (5.23 per 1000 vaccinated individuals, 95% CI: 1.7-12.2) and the ACAM2000 clinical trial outcomes for symptomatic persons, which was 2.29 per 1000 vaccinated individuals (95% CI: 0.3-8.3). CONCLUSIONS: Vaccination with ACAM2000 is the presumptive cause of this cluster. Caution should be exercised before considering vaccination campaigns for smallpox given the clinical morbidity and costs incurred by a case of myopericarditis. Risk of myopericarditis should be carefully weighed with risk of exposure to smallpox.

Primary eosinophilic lung diseases.

Eosinophilic lung diseases typically present as a triad of pulmonary symptoms, an abnormal chest radiograph, and elevated levels of eosinophils in the sputum and lung tissue. This article focuses on primary causes of eosinophilic lung disease including acute eosinophilic pneumonia, chronic eosinophilic pneumonia, Churg-Strauss syndrome, and hypereosinophilic syndromes. In these disorders elevated eosinophil levels in the tissue lead to inflammation and tissue damage. Peripheral eosinophilia can often be measured when tissue levels are elevated but this is not as reliable a marker as tissue biopsy. Because corticosteroids act through a variety of mechanisms to inhibit eosinophil function and induce apoptosis, they are first-line therapy for eosinophilic lung diseases. Targeted immunosuppressive therapies, such as monoclonal antibodies against key regulatory cytokines for eosinophil production and survival, are not formally approved for eosinophilic lung disease but have shown promising results in published research studies.

Adverse events following smallpox vaccination with ACAM2000 in a military population.

BACKGROUND: Generalized vaccinia and benign exanthems are 2 adverse events that have been associated with the smallpox vaccination. Accurate incidence and prevalence rates of each are not readily available, but these events are thought to be uncommon. To our knowledge, this is the first case series to provide clinical as well as pathologic descriptions of multiple papulovesicular eruptions occurring after receiving the second-generation smallpox vaccine, ACAM2000 (Acambis, Canton, Massachusetts), among a vaccinia-naïve military population. In addition, we report the first confirmed case, to our knowledge, of generalized vaccinia following administration of the ACAM2000 vaccine. OBSERVATIONS: All patients received primary smallpox immunization as well as 1 to 3 concurrent or near-concurrent (within the preceding 21 days) immunizations for typhoid, anthrax, hepatitis B, and/or seasonal influenza. One patient presented with a flulike prodrome and diffuse vesiclopustules covering the face, neck, chest, back, and upper and lower extremities. Vaccinia polymerase chain reaction confirmed generalized vaccinia. The remaining 7 patients presented with unusual, painful, and pruritic papulovesicular eruptions occurring on the extensor surfaces of their upper and lower extremities without systemic symptoms. Histologic findings revealed 2 general patterns, including a dermal hypersensitivity reaction with lymphocytic vasculitis and a vesicular spongiotic dermatitis with eosinophils. CONCLUSIONS: We present the first confirmed case of generalized vaccinia following immunization with the second-generation smallpox vaccine ACAM2000. In addition, we describe 7 cases of benign, acral, papulovesicular eruptions thought to be associated with ACAM2000 administration. Further research is needed to discern the pathogenesis of these benign eruptions as well as their incidence and prevalence and that of generalized vaccinia with ACAM2000.

Determination of the incidence of sensitization after penicillin skin testing.

BACKGROUND: Concerns for sensitization after penicillin skin testing are a factor in limiting the timing and population for whom this testing is offered. The sensitizing potential of the penicillin skin test has never been studied directly. METHODS: A total of 329 volunteers underwent prick and intradermal skin testing with penicillin G, benzylpenicilloyl-polylysine, and a minor determinant mixture. Those with negative skin testing had repeat testing 4 weeks later. Medical history and antibiotic use were determined by interview, questionnaire, and electronic pharmacy records. RESULTS: Seventy-two of the 329 subjects (22%) reported a history of previous beta-lactam reaction, of which 10 (14%) had a positive initial skin test. Overall, the initial skin test was positive in 23 of 329 (7%). Of the subjects with a negative initial skin test, 239 completed the second test 4 weeks later. Of these, 6 subjects (2.5%, 95% confidence interval 0.5% to 4.5%) converted to a positive skin test. None had taken a beta-lactam antibiotic between the two tests, and none had any previous history of beta-lactam reaction. One subject reported having never taken a beta-lactam antibiotic before. In comparison to the 233 subjects who did not convert their skin test, the statistically significant factors favoring sensitization were: female sex (odds ratio [OR] 6.53, P = 0.05), atopy (OR 5.31, P = 0.04), and history of food allergy (OR 6.35, P = 0.02). There was a trend toward more recent penicillin use in the newly sensitized subjects, but this was not statistically significant.. CONCLUSION: Penicillin skin testing may sensitize a small number of individuals to penicillin.