What are the differentials for a sore arm persisting three months after a Tetanus, diphtheria, and pertussis (Tdap) vaccination?

Differential Diagnosis for Persistent Arm Pain Three Months Post-Tdap Vaccination

A sore arm persisting three months after Tdap vaccination is abnormal and requires evaluation beyond typical vaccine reactions, as documented adverse events from tetanus-containing vaccines resolve within days to weeks, not months.

Expected Vaccine Reactions (Now Excluded by Timeline)

The typical local reactions to Tdap vaccines resolve much faster than three months:

• Acute injection site reactions (pain, redness, swelling) occur in 19-38% of recipients but resolve within 3-14 days 1
• Extensive limb swelling (entire upper arm involvement) occurs in 2-3% of booster recipients, begins within 48 hours, and resolves completely within 3-10 days without sequelae 1, 2
• Increased reactogenicity with booster doses shows pain in up to 38% and swelling >5 cm in up to 31%, but duration remains limited to days 1

Critical point: Even the most severe documented vaccine-related reactions (entire limb swelling) resolve within 1-2 weeks maximum 1, 2. Three-month persistence indicates a different pathology.

Primary Differential Diagnoses to Consider

1. Shoulder Injury from Injection Technique (SIRVA)

• Inadvertent injection into the shoulder joint capsule, bursa, or rotator cuff rather than deltoid muscle
• Presents with persistent pain, limited range of motion, and functional impairment lasting months
• Most likely diagnosis given temporal relationship to injection and prolonged symptoms
• Requires imaging (MRI or ultrasound) to identify bursitis, tendinitis, or capsulitis

2. Injection Site Abscess or Chronic Infection

• Rare but possible with contamination or improper technique
• Would present with persistent pain, possible warmth, induration, or fluctuance
• Requires ultrasound evaluation to identify fluid collection
• May need aspiration for culture and drainage

3. Nerve Injury (Radial or Axillary Nerve)

• Direct needle trauma or compression from inflammatory reaction
• Presents with persistent pain, paresthesias, weakness, or altered sensation
• Distribution of symptoms helps localize: radial nerve (wrist drop, dorsal hand numbness) vs. axillary nerve (deltoid weakness, lateral shoulder numbness)
• May require nerve conduction studies and EMG

4. Complex Regional Pain Syndrome (CRPS) Type I

• Disproportionate pain following minor trauma (injection)
• Associated with allodynia, temperature changes, swelling, skin changes
• Diagnosis is clinical based on Budapest criteria
• Requires early aggressive physical therapy and pain management

5. Rotator Cuff Pathology (Pre-existing, Exacerbated)

• Injection may have unmasked or worsened underlying shoulder pathology
• Persistent pain with overhead activities, night pain
• Physical examination shows positive impingement signs, weakness with specific movements
• MRI confirms diagnosis

6. Deltoid Muscle Injury or Myositis

• Direct trauma from injection or inflammatory myopathy
• Persistent localized pain and weakness
• Elevated creatine kinase if significant muscle injury
• Ultrasound or MRI shows muscle edema or tear

Less Likely but Reportable Considerations

7. Autoimmune/Inflammatory Response

• Rare vaccine-triggered autoimmune phenomena (e.g., POTS has been reported post-dTdap) 3
• Would typically present with systemic symptoms beyond local arm pain
• Consider if constitutional symptoms present

8. Arthus-Type Hypersensitivity Reaction

• Immune complex-mediated reaction from high pre-existing antibody levels
• Typically occurs within hours and resolves within weeks, not months 4
• Three-month duration makes this unlikely

Diagnostic Approach

Immediate evaluation should include:

• Detailed pain characterization: location (deltoid vs. shoulder joint), quality (sharp, burning, aching), aggravating factors (movement patterns, position), associated symptoms (weakness, numbness, temperature changes)
• Range of motion assessment: active and passive shoulder movement in all planes, comparing to contralateral side
• Neurological examination: motor strength testing (deltoid, rotator cuff, wrist/finger extensors), sensory mapping (axillary, radial nerve distributions), reflexes
• Injection site inspection: residual erythema, warmth, induration, fluctuance, skin changes suggesting CRPS
• Functional assessment: ability to perform overhead activities, lifting, dressing

Initial imaging:

• Shoulder ultrasound as first-line to evaluate for fluid collections (abscess, bursitis), rotator cuff integrity, and deltoid muscle pathology
• MRI shoulder if ultrasound inconclusive or SIRVA suspected, to definitively assess bursa, joint capsule, rotator cuff, and bone marrow edema

Laboratory testing (if indicated by examination):

• Creatine kinase if myositis suspected
• CBC, ESR, CRP if infection or inflammatory process considered
• Blood cultures only if systemic signs present

Critical Management Pitfall

Do not dismiss prolonged post-vaccination symptoms as "normal vaccine reactions." The evidence clearly demonstrates that even extensive limb swelling from DTaP/Tdap resolves within days 1, 2. Three-month persistence mandates investigation for structural injury, particularly SIRVA, which is an increasingly recognized and compensable vaccine injury requiring prompt diagnosis and treatment to prevent chronic disability.