Pathological skin manifestations following smallpox vaccination (ACAM2000) in US military personnel, 2009-2023: a systematic review

In the aftermath of anthrax bioterrorism, the US military began its smallpox immunization program in 2002. Dryvax was superseded in 2008 by ACAM2000, a second-generation smallpox vaccine, after clinical trials demonstrated favorable outcomes. However, these trials focused on significant adverse effects and provided less specific classifications and descriptions of cutaneous eruptions. The purpose of this systematic review was to investigate the clinicopathological characteristics of skin lesions that emerged in US military personnel following the reinstatement of new smallpox immunizations. PubMed, ScienceDirect, and Google Scholar were searched. The search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using appropriate keywords. Of the 467 studies initially identified, 5 (1%) were analyzed, with a sample size of 15. There were 10 men and 4 women. The mean age of presentation was 24.3 years. The interval between inoculation and eruption was 15 days. The length of the eruption until clearance was 36.26 days. Grossly, most skin lesions were described as having papules (n = 9). Histological examination revealed vesicles with spongiotic dermatitis and eosinophils (n = 5) and a dermal hypersensitivity reaction with lymphocytic vasculitis (capillaritis) (n = 2). Definitive diagnoses included acral and vesiculopustular dermatosis (n = 7), generalized vaccinia (GV) (n = 1), and progressive vaccinia (n = 1). Concurrent or near-concurrent vaccination was administered (n = 12). Although rare, clinically significant skin lesions can occur after ACAM2000 administration. A feared complication of progressive vaccinia has been reported; however, to determine its causal relationship, further clinical trials are required to provide universal guidelines.