What are the potential side effects of the flu vaccine, particularly in high-risk populations such as the elderly or those with compromised immune systems or chronic illnesses?

Side Effects of Flu Vaccine

Influenza vaccines are safe and well-tolerated with predominantly mild, self-limited local reactions; the most common side effect is injection-site soreness lasting up to 2 days, while systemic symptoms occur no more frequently than placebo, and serious adverse events are exceedingly rare. 1, 2

Common Local Reactions

• Injection-site pain, redness, and swelling are the most frequent adverse effects, occurring in approximately 64% of vaccine recipients compared to 24% with placebo 3
• Local soreness typically lasts up to 2 days, is generally mild and not disabling, and rarely results in decreased arm use 2, 3
• Inactivated influenza vaccines (IIVs) may be more likely to cause injection-site reactions than live attenuated vaccines (LAIVs) 1
• Extensive limb swelling extending beyond the shoulder or elbow occurs rarely (26 reports over three seasons in one surveillance system), resembles cellulitis, and usually resolves with symptomatic treatment 4

Systemic Symptoms

• Systemic symptoms including fever, malaise, headache, and myalgias occur at the same rate as placebo (approximately 34-35%) 3
• When systemic symptoms do occur, they typically begin 6-12 hours after vaccination and last 1-2 days 2
• Flu-like illness may be reported 5.5% more frequently in the first week post-vaccination compared to baseline, but these symptoms do not result in decreased ability to perform daily activities 5
• Fatigue, headache, and myalgia are the most common systemic effects in adults and elderly persons 1

Age-Specific Considerations

Children

• Fever and febrile seizures are more common in children than adults 6
• Some studies report a modest increase in febrile seizures in young infants when influenza vaccine is given with other vaccines, though most studies find no association 1
• Live attenuated vaccines (nasal spray) may cause nasal congestion, headache, myalgias, or fever 7
• LAIVs are contraindicated in children under 2 years due to increased risk of wheezing 7

Elderly and High-Risk Populations

• The vaccine has a robust safety profile in older adults and those with chronic diseases, with injection-site pain being the most common local effect 1
• High-dose vaccines in adults ≥65 years may cause minimally increased mild local reactions, but this is far outweighed by enhanced protection 2
• Among chronically ill older persons (mean age 63), only 5.3% reported fever and 10.4% reported disability within one week of vaccination—rates similar to unvaccinated controls 5

Immunocompromised Patients

• Influenza vaccines are safe in immunocompromised populations including HIV-infected persons, transplant recipients, and those on immunosuppressive therapy 1
• Only inactivated or recombinant vaccines should be used in immunocompromised patients—never live attenuated vaccines 1, 8

Rare Serious Adverse Events

Guillain-Barré Syndrome (GBS)

• GBS was clearly associated only with the 1976 swine influenza vaccine and has not been definitively linked to influenza vaccines since then 2, 9
• The risk of vaccine-associated GBS, if any, is estimated at most 1-2 cases per 1 million vaccinees 7
• One Italian case-control study (2010-2011) identified a small but significant association (1.03 GBS admissions per million vaccinations), but this risk was substantially lower than GBS risk from influenza infection itself (17.2 per million influenza encounters) 1

Allergic Reactions

• Rare immediate allergic reactions can occur in patients with egg hypersensitivity, as vaccines are grown in eggs 2
• Anaphylaxis, angioedema, and severe acute reactions are exceedingly rare (3 reports over three seasons in one surveillance system) 4

Critical Safety Context

• The vaccine does not contain live virus (except LAIV) and cannot cause influenza infection 2, 9
• Over three influenza seasons, only 6% of adverse event reports were considered "serious" (mostly hospitalizations), and deaths reported had unlikely causal relationship to vaccination 4
• Female sex, age <40 years, and coincidental upper respiratory illness are independently associated with higher rates of systemic symptoms—not the vaccine itself 3

Special Population Contraindications

Live Attenuated Vaccines (LAIV) Should NOT Be Used In:

• Immunosuppressed individuals and their close contacts 1
• Pregnant women 1
• Children under 2 years and adults over 50 years 1
• Children ages 2-4 with history of recurrent wheezing or reactive airways disease 7
• Patients with chronic pulmonary conditions 8, 9

Common Pitfalls to Avoid

• Do not assume the vaccine causes influenza illness—the inactivated vaccine cannot replicate and systemic symptoms occur at placebo rates 2, 3
• Do not delay vaccination in high-risk patients due to concerns about side effects—the mortality reduction (68-80% in elderly) and hospitalization prevention (30-70%) far outweigh minimal adverse effects 9
• Do not extrapolate safety of one influenza vaccine type to all types, especially in children—each requires safety testing in the target age group 6
• Do not use live attenuated vaccines in immunocompromised patients or those with chronic conditions—only inactivated or recombinant formulations are appropriate 1, 8