JAMA, The Journal of the American Medical Association
Wednesday, May 25, 1994
Vol. 271, No. 20, ISSN: 0098-7484

Adverse reactions to tetanus toxoid. (Questions and Answers)
John R. Agnew Roland W. Sutter

Q A patient, previously immunized in the military, received a tetanus toxoid booster vaccination that resulted in a painful,
erythematous upper extremity, with several days of fever and lassitude. If he has a penetrating injury in the future, what should
be done?

John R. Agnew, MD

Fort Myers, Fla

A Although few details of this patient's adverse event following vaccination are available, in general, adverse reactions following
tetanus toxoid may be influenced by the number of previous doses, the toxoid dosage, the route and method of administration,
and the presence of adjuvants and/or other antigens (such as diphtheria toxoid) in the preparation chosen. The most common
adverse event following tetanus booster vaccination (in 50% to 85% of recipients) is a local reaction characterized by pain and
tenderness at the injection site, less frequently (in 20% to 30%) followed by edema and erythema, and rarely (less than 2%)
marked by considerable swelling.[1] Several studies have found a direct correlation between the circulating tetanus antitoxin
level and the degree of local reaction. A few reports have described massive local reactions (eg, associated with swelling from
elbow to shoulder), occurring primarily in persons receiving multiple booster doses of toxoid. Generally, these reactions begin
within 2 to 8 hours after the injection. Circulating antibody apparently forms complexes with the deposited toxoid to induce an
inflammatory response (Arthus reaction, type II hypersensitivity). Fever can accompany a local response (in 0.5% to 7%),
particularly when local reaction is marked or antitoxin levels are high, or both. However, a temperature higher than
39[degrees]C is rare, and other systemic symptoms, such as headache or malaise, are rarely reported. The preservative used in
tetanus toxoid (ie, thimerosal) can lead to delayed-type hypersensitivity, while serum-sicknesslike illnesses appear to be rarely
associated with tetanus toxoid.

This patient most likely experienced an Arthus-type reaction, probably caused by multiple previous doses of the toxoid that
resulted in high levels of circulating tetanus antitoxin. Assessment of tetanus antitoxin levels could substantiate the diagnosis and
assist future management in the event of a penetrating injury. If high levels of tetanus antitoxin are found, the patient should be
protected for at least 10 years, and tetanus toxoid should not be administered during this period. If tetanus antitoxin levels are
low, the patient should be evaluated by an immunologist or allergist; tetanus immunoglobulin could be used in the event of a
tetanus-prone wound to provide short-term protection until tetanus toxoid can be safely administered. To prevent such
reactions, tetanus toxoid should not be administered routinely more frequently than every 10 years as recommended by the
Advisory Committee on Immunization Practices.[2]

To better monitor the risk and nature of serious adverse events following vaccination (including vaccination with tetanus toxoid),
physicians are requested to report these events to the Vaccine Adverse Event Reporting System. Report forms and additional
information on reporting may be obtained by telephoning (800) 822-7967.

Roland W. Sutter, MD, MPH&TM

National Immunization Program
Centers for Disease Control and Prevention

Atlanta, Ga [1.] Wassilak SGF, Orenstein WA, Sutter RW. Tetanus toxoid. In: Plotkin SA, Mortimer EA, eds. Vaccines. 2nd
ed. Philadelphia, Pa: WB Saunders Co. In press. [2.] Centers for Disease Control. Diphtheria, tetanus, and pertussis:
recommendations for vaccine use and other preventive measures. MMWR Morb Mortal Wkly Rep. 1991;40(RR-10):1-28.