Acute Disseminated Encephalomyelitis Following Influenza Vaccine (2014)

To the Editors: Acute disseminated encephalomyelitis is an immune-mediated inflammatory demyelinating disease of the central nervous system, usually preceded by an infection.1 In about 5% of the cases, the only known risk factor is a vaccination received within a month before the onset of the symptoms.1 Data from the US-based Vaccine Adverse Event Reporting System and the European Union-based Eudravigilance safety databases indicate that, along with the human papilloma virus, the vaccines against seasonal influenza and H1N1 are the most frequently reported to be associated with acute disseminated encephalomyelitis onset.2 Although the incidence of acute disseminated encephalomyelitis after several types of vaccinations has been reported,1–4 there is still a lack of data on the incidence of this condition after vaccines against seasonal influenza or H1N1. In this analysis, we estimated the incidence of acute disseminated encephalomyelitis occurring after vaccination against H1N1 and seasonal influenza in the United States. Data on vaccine coverage were retrieved from the Centers for Disease Control website (http://www.cdc.gov/flu/index.htm) and cases from the Vaccine Adverse Event Reporting System database, according to previously described procedures.2 We retrieved 60 cases that occurred after vaccination against influenza (from season 2006–2007 to season 2013–2014) and 12 cases after vaccination against H1N1. As shown in the Figure, the mean incidence of acute disseminated encephalomyelitis after vaccination against influenza was estimated to be 0.05 per million doses, ranging between 0.03 (season 2011–2012) and 0.09 (season 2007–2008), without major variations among seasons. The incidence after the H1N1 vaccine was instead considerably higher (0.15 cases per 1,000,000).FIGURE: Annual Incidence (per Million) of Acute Disseminated Encephalomyelitis Following Seasonal Influenza Vaccines, with 95% Confidence Intervals.These estimates are in line with previously reported data on the incidence of acute disseminated encephalomyelitis after other vaccines. After administration of the live measles vaccine, acute disseminated encephalomyelitis was reported to occur in about 1 to 2 cases per million, whereas the smallpox vaccine was estimated to cause 4.5 cases per million in the United States (3/665,000).5 A similar analysis, based on the review of postmarketing surveillance in Japan, estimated an incidence of 2 cases per million.6 The incidence of acute disseminated encephalomyelitis after the diphtheria–pertussis–tetanus vaccine has been estimated as 9 cases per million.7 Two recent analyses carried out among US adolescent found lower incidence, 0.05 cases per million doses after administration of adult tetanus, diphtheria, or acellular pertussis vaccines8 and 0.26 cases per million doses after vaccination against the human papillomavirus.3 The absence of large differences between reported rates after vaccination in the various influenza seasons is notable. The results of our analysis indicate that the number of reported acute disseminated encephalomyelitis cases per million was higher for the H1N1 vaccines. This result may derive from the higher attention toward adverse reactions after the introduction of these vaccines, resulting in a higher probability of adverse events thought to be associated with vaccination and therefore reported.2,4 Our results indicate that the incidence of postvaccine acute disseminated encephalomyelitis is very low, especially among patients who receive vaccination against seasonal influenza. The efficacy of influenza vaccines largely surpasses the risk of developing postvaccine acute disseminated encephalomyelitis. Paolo Pellegrino Sonia Radice Unit of Clinical Pharmacology Department of Biomedical and Clinical Sciences University Hospital Luigi Sacco Università di Milano Milan, Italy [email protected] Emilio Clementi Unit of Clinical Pharmacology Department of Biomedical and Clinical Sciences Consiglio Nazionale delle Ricerche Institute of Neuroscience University Hospital Luigi Sacco Università di Milano Milan, Italy Scientific Institute IRCCS E. Medea Lecco, Italy