Postvaccination Adverse Events

It's important to keep an open mind when a parent informs you that his or her child has experienced an adverse event following vaccination.

Determining which adverse events are caused by a vaccine and which are mere coincidental associations can be very difficult. As physicians who administer vaccines to children, one of the most important contributions we can make is to report all postimmunization adverse events to the Vaccine Adverse Events Reporting System (https://vaers.hhs.gov/index

The best information we have comes from studies that compare population-based rates of a specific event with the postimmunization rates to see if there is a significant difference. Alternatively, case-control studies can identify whether the odds ratio for receipt of a vaccine is increased among cases. Unfortunately, such studies have been done for only a fraction of all reported postvaccination adverse events.

I'd like to highlight a few prominent adverse events that have been reported following immunization. Some, although unusual, have been causally linked to vaccines. Others, particularly certain severe neurologic outcomes, do not appear to be linked although monitoring continues.

▸ Thigh swelling and the DTaP vaccine. This one is fairly well established. Often confused with cellulitis, swelling of the entire arm or leg following receipt of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is reported in nearly 2% of all children following the fourth dose, with rates and severity increasing with each successive DTaP dose (Pediatr. Infect. Dis. J. 2008;27:464-5).

However, unlike cellulitis, it is rarely associated with fever or other systemic symptoms, is localized to the vaccinated limb, and usually resolves completely within 48 hours. Although the swelling is likely to occur again with subsequent doses, both the CDC's Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics recommend that the child receive all recommended DTaP doses following appropriate counseling of the parents.

▸ Hair loss and the hepatitis B (and other) vaccines. There have been 60 case reports of hair loss (alopecia) following receipt of vaccines, 46 of them associated with the hepatitis B vaccine. These included 16 in which the hair grew back but then fell out again after re-vaccination. Nine of the patients reported previous medication allergy (JAMA 1997;278:1176-8). This appears to be a true causal effect, although rare considering the tens of millions of hepatitis B doses given over the last decades. But in a small number of genetically predisposed children – most of them female – there does appear to be biological plausibility because hair loss has recurred with second dose and is further supported by the several case reports of alopecia in chronic active hepatitis B viral infection patients.

▸ Idiopathic thrombocytopenic purpura and MMR vaccine. This link is probably also causal. One study utilizing immunization and hospital admission records demonstrated an absolute risk of one case in every 22,300 doses within 6 weeks of MMR vaccination (Arch. Dis. Child. 2001;84:227-9). Another study, which attempted to control for the effect of viral infections, found a similar idiopathic thrombocytopenic purpura (ITP) risk of about 1 in 30,000 MMR immunizations. That population-based analysis of 506 consecutive pediatric ITP patients also found that the thrombocytopenia disappeared within a month in 74% of patients and lasted longer than 6 months in only 10% (Vaccine 2007;25:1838-40).

▸ Myocarditis after vaccination. Inflammatory myocarditis was reported in 10 of approximately 240,000 military recipients of the smallpox vaccine and in 2 additional civilian cases during the widespread pre-event immunization program in 2001. Although it was not definitively linked to the vaccine, ACIP nonetheless recommended that those with heart disease or at risk for it should not receive the vaccine (MMWR 2003;52:282-4).

In children, there have been two reported cases of myocarditis following immunization, one following the hepatitis B vaccine in a previously healthy 12-year-old girl, the other after receipt of meningococcal C conjugate vaccine in a 14-year-old boy. Both showed eosinophilic infiltrates on myocardial biopsies, consistent with an allergic reaction to the vaccine (Pediatr. Infect. Dis. J. 2008;27:831-5). I think the jury is still out on this one. Certainly if you see a case, be sure to report it to VAERS.

▸ Acute disseminated encephalomyelitis and vaccination. These reports have been coming in since the 1970s, for a variety of different vaccines. Examples include Guillain-Barré syndrome (GBS) following the Haemophilus influenzae B conjugate vaccine (Eur. J. Pediatr. 1993;152:613-4), central nervous system inflammatory demyelination following hepatitis B vaccination (Neurology 2009;72:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42:155-9).

Without knowing the background rates of these neurologic complications among unvaccinated individuals, it is impossible to ascertain causality. An excellent data analysis conducted by Dr. Steven Black and colleagues provided very helpful estimates of the numbers of specific severe adverse events that would be expected following receipt of the 2009 H1N1 influenza vaccine.