What are the differentials for pain and swelling in the left axilla (armpit) area approximately 48 hours after receiving the influenza (flu) and herpes zoster (shingles) vaccines?

Differential Diagnosis for Left Axillary Pain and Swelling 48 Hours Post-Vaccination

The most likely diagnosis is reactive lymphadenopathy (vaccine-associated adenopathy), a well-recognized benign immune response to intramuscular vaccination that typically manifests within 2-4 days and resolves within 1-2 weeks. 1

Primary Differential Diagnoses

1. Reactive Lymphadenopathy (Most Likely)

• Vaccine-associated adenopathy occurs in up to 16% of vaccine recipients aged 18-64 years and represents the normal immune response to intramuscular deltoid injection 1
• Lymph node enlargement results from locally activated antigens that accumulate at the injection site and migrate to draining axillary and supraclavicular nodes 1
• The 48-hour timeline perfectly matches the expected onset of 2-4 days post-vaccination 1
• Both influenza and herpes zoster vaccines are documented to cause regional adenopathy, with influenza vaccine specifically showing increased nodal metabolic activity on imaging 1
• Clinical duration typically ranges from 1-2 days (Moderna data) to 10 days (Pfizer data), though imaging findings may persist longer 1

2. Injection Site Reaction with Extension

• Pain, redness, and swelling occur in 19-38% of vaccine recipients but typically resolve within 3-14 days 2
• Extensive limb swelling can occur in 2-3% of booster recipients, beginning within 48 hours 2
• The reaction may extend beyond the immediate injection site to involve regional lymphatic drainage 2

3. Arthus Reaction (Type III Hypersensitivity)

• Characterized by pain, swelling, induration, and edema at or near injection sites, representing immune complex-mediated inflammation 3
• More commonly occurs after repeated vaccinations (50% of cases occur after second dose, 23.3% after third dose) 3
• Can occur after first dose in 13.3% of cases if pre-existing specific IgG antibodies are present 3
• Generally self-limited and resolves without treatment in mild cases 3

4. Nerve Injury (Less Likely at 48 Hours)

• Radial or axillary nerve damage from direct needle trauma or compression from inflammatory reaction 2
• Would typically present with persistent pain, paresthesias, weakness, or altered sensation beyond simple swelling 2
• Less consistent with the 48-hour timeline and bilateral vaccine administration scenario 2

5. Deltoid Muscle Injury or Myositis

• Direct trauma from injection or inflammatory myopathy presenting with localized pain and weakness 2
• Would be expected at the deltoid injection site rather than primarily axillary 2

Critical Clinical Assessment Points

Examination Findings to Evaluate

• Assess for warmth, tenderness, and erythema overlying the swelling to distinguish infectious from reactive causes 4
• Palpate for discrete lymph nodes versus diffuse tissue swelling 4
• Evaluate for fluctuance indicating abscess formation (would require drainage) 4
• Check for signs of systemic toxicity including fever >38°C, tachycardia, or altered mental status 4
• Assess functional limitation: ability to perform overhead activities, lifting, and dressing 2
• Examine the injection site itself for local reaction characteristics 2

Red Flags Requiring Further Investigation

• Fever, systemic symptoms, or signs of toxicity suggest infection rather than reactive adenopathy 4
• Rapidly progressive swelling beyond expected vaccine reaction timeline 4
• Severe pain requiring prescription medication (occurred in 0.3-0.6% of vaccine recipients) 1
• Persistent symptoms beyond 2 weeks warrant imaging evaluation 1

Diagnostic Approach

Initial Management (First 2 Weeks)

• Reassurance and observation are appropriate for typical vaccine-associated adenopathy presenting within 2-4 days of vaccination 1
• Symptomatic treatment with NSAIDs or acetaminophen for pain management 3
• No imaging is indicated for typical presentations in the first 1-2 weeks 1

When to Pursue Further Workup

• If symptoms persist beyond 10-14 days, ultrasound is the initial imaging modality to differentiate solid lymph nodes from abscess 4
• Laboratory testing (CBC, ESR, CRP) if infection or inflammatory process is suspected based on fever or systemic symptoms 4, 2
• CT with contrast reserved for suspected deep space infection or when ultrasound is inconclusive 4

Important Clinical Pitfalls

Cancer Screening Considerations

• In patients with cancer history or undergoing cancer surveillance, vaccine-associated adenopathy can mimic metastatic disease, leading to unnecessary biopsies or treatment changes 1, 5
• This is particularly relevant for breast cancer, head and neck cancers, lymphoma, and melanoma of upper extremities 1
• Ideally, cancer-related imaging should be performed prior to vaccination when feasible 1
• For routine surveillance or screening (not urgent indications), consider postponing imaging for 4-6 weeks post-vaccination 1

Documentation Requirements

• Document which arm received which vaccine, as adenopathy should be ipsilateral to the injection site 1
• If both vaccines were given in the left arm, this strongly supports reactive adenopathy as the diagnosis 1

Rare Long-Term Complications

• One case report documented prolonged joint pain and neurological symptoms persisting over one year following Shingrix vaccination, though this is exceptionally rare 6
• Most vaccine reactions resolve completely within days to weeks without sequelae 1, 2, 3