Anaphylaxis to simultaneous administration of inactivated tissue culture hepatitis A vaccine and purified chick embryo cell rabies vaccine after multiple doses

Background

Anaphylaxis is a serious and fatal systemic allergic reaction that occurs after exposure to an allergen, which may be caused by food, drugs or vaccination.1 Anaphylaxis occasionally returns after an asymptomatic period without further exposure to the causative antigen (biphasic reaction). Anaphylaxis after vaccination rarely occurs, in the analysis performed by McNeil and colleagues, the incidence rate was 1.31 episodes per 1 million vaccinations.2 In the analysis performed by John R Su and colleagues, 40% of patients with anaphylaxis have never had any allergies to foods, drugs or so on.3

In Japan, Aimmugen, a freeze-dried inactivated tissue culture hepatitis A vaccine (HAV) has been approved. Three doses of Aimmugen are generally required to complete the HAV series. In the prospective study performed by Endo and colleagues, the seroconversion rate was reported to be 94.4% for two doses and 100% for three doses.4 HAV is recommended when travelling to high risk areas such as Southeast Asia, South America and Africa.5

Rabipur is a purified chick embryo cell rabies vaccine (PCECV) for pre-exposure and postexposure prophylaxis (PEP) against rabies virus and was approved in Japan in March 2019. Two doses of pre-exposure vaccination against rabies are recommended before travel to high-risk areas in addition to the HAV,6 7 whereas Ministry of Health, Labour and Welfare (MHLW) recommend three doses pre-exposure rabies prophylaxis.8

Here, we report a case of anaphylaxis that occurred after sequential doses of Aimmugen and Rabipur in a 24-year-old man with no known history of allergies.

Case presentation

A 24-year-old Japanese man visited our travel clinic before his trip to South Africa 3 months later. He has been treated for ulcerative colitis with mesalazine and had a history of tonsillectomy for IgA nephropathy during his childhood. He took no other medication. He had no history of allergy to any drug, vaccine or foods. He had already been given usual vaccines such as diphtheria, tetanus, pertussis, measles, rubella, mumps, Bacille Calmette-Guérin, Japanese encephalitis and hepatitis B vaccine. We scheduled to give Rabipur and Aimmugen as pretravel vaccinations. The inactivated typhoid vaccine was also considered, but it was not given since it is not approved in Japan. The first doses of both vaccines were given on day X-28, and no adverse events occurred. On day X-21, the second dose of Rabipur was administered. On day X, he received the second dose of Aimmugen and the third dose of Rabipur .

Ten minutes after the vaccinations, he felt sick and reported itchiness of the face, abdominal pain and sore throat. On physical examination, he was alert and oriented. His blood pressure was 150/70 mm Hg, heart rate was 90 bpm, respiratory rate was 16/min, oxygen saturation was 98% on room air and body temperature was 36.8°C at axillary measurement. There was urticaria on his face. There were no abnormal respiratory sounds such as wheeze or stridor. There was slight tenderness on the entire abdomen. A few minutes later, his blood pressure dropped to 90/60 mm Hg and pulse rate increased from 90 bpm to 100 bpm.

Since he did not have any food or medications before vaccinations, diagnosis of anaphylaxis secondary to Aimmugen or Rabipur or the combination was made. We immediately administered 0.3 mg of intramuscular epinephrine to the mid-outer aspect of the thigh. After that, famotidine and methylprednisolone were given intravenously.

Outcome and follow-up

Shortly after the injection, urticaria disappeared and abdominal pain was improved. He was admitted for close observation. Since the biphasic reaction did not occur, he was discharged home the next day. Epinephrine for intramuscular injection was prescribed to prevent further anaphylaxis if receiving rabies vaccination for PEP after animal exposure abroad.

With regards to HAV, our patient had already received two doses of Aimmugen and the antibody titre might be sufficiently elevated. A third dose would be administered to further increase the seroconversion rate. However, because Aimmugen was also the suspected vaccine for anaphylaxis, we did not give the third dose.