What are the differential diagnoses for arm weakness and hand discoloration in a 35‑week pregnant woman one day after receiving a tetanus, diphtheria, and acellular pertussis (Tdap) vaccine?

Differential Diagnoses for Arm Weakness and Hand Discoloration After Tdap at 35 Weeks Gestation

The most likely diagnosis is a local injection site reaction with possible extensive limb swelling, though you must urgently rule out compartment syndrome, deep vein thrombosis, and neurologic complications such as brachial neuritis. 1, 2

Most Likely Vaccine-Related Diagnoses

Local Injection Site Reactions with Extensive Limb Swelling

• Pain, swelling, and discoloration are common after Tdap, occurring in up to 79% of pregnant recipients for pain and 7.6% for swelling. 3
• Extensive limb swelling can occur after tetanus toxoid-containing vaccines and typically resolves within 4-7 days without complication. 1
• The "tired arms" likely represent significant injection site pain and myalgia, which are expected adverse effects. 3, 4
• Hand discoloration may result from dependent edema and venous congestion secondary to proximal arm swelling. 1

Arthus Reaction (Type III Hypersensitivity)

• This is a severe local vasculitis characterized by severe pain, swelling, induration, edema, hemorrhage, and occasionally local necrosis. 1
• Onset is typically 4-12 hours after vaccination (not immediate like anaphylaxis). 1
• More likely if the patient received a prior tetanus-containing vaccine within the past 2-5 years, as high preexisting antibody levels increase risk. 1
• The discolored hands could represent hemorrhagic changes extending distally from the injection site. 1

Critical Neurologic Differentials to Rule Out

Brachial Neuritis (Parsonage-Turner Syndrome)

• Tetanus toxoid-containing vaccines have a causal relationship with brachial neuritis, with a relative risk of 5-10 compared to background incidence. 2
• Presents with severe shoulder and arm pain followed by weakness and atrophy of shoulder girdle muscles. 1, 2
• Onset is typically days to weeks after vaccination. 2
• The "tired arms" could represent early motor weakness rather than simple fatigue. 1

Guillain-Barré Syndrome (GBS)

• While exceedingly rare (1 case when 2 expected by chance in 1.2 million doses), GBS has a possible causal relationship with tetanus toxoid-containing vaccines. 1, 2
• Presents with ascending weakness, paresthesias, and autonomic dysfunction. 1
• Onset is typically within 6 weeks of vaccination. 1, 2
• Bilateral arm weakness would be concerning for early GBS. 1

Vascular/Thrombotic Differentials

Deep Vein Thrombosis (DVT)

• Pregnancy is a hypercoagulable state, and DVT risk increases throughout gestation. 5
• Arm swelling with discoloration could represent upper extremity DVT. 5
• Large safety studies found no increased risk of venous thromboembolic events after Tdap in pregnancy, with slightly decreased rates in some cohorts. 5
• However, this remains a critical diagnosis to exclude given the timing and symptoms. 5

Compartment Syndrome

• Though rare, severe injection site swelling could theoretically progress to compartment syndrome. 1
• Presents with severe pain, paresthesias, weakness, and pallor/discoloration. 1
• This is a surgical emergency requiring immediate fasciotomy if confirmed. 1

Pregnancy-Related Differentials

Preeclampsia with Peripheral Edema

• At 35 weeks, preeclampsia is a critical consideration for any new-onset swelling. 6
• However, preeclampsia typically presents with bilateral lower extremity edema, not isolated upper extremity involvement. 6
• One large study found a slightly increased adjusted relative risk of 1.38 for preeclampsia after Tdap, though this was consistent with background trends and did not exceed the safety threshold. 6

Carpal Tunnel Syndrome (Pregnancy-Related)

• Common in late pregnancy due to fluid retention and median nerve compression. 5
• Could cause hand paresthesias and perceived "tiredness" but would not explain discoloration. 5

Immediate Clinical Approach

History to Obtain

• Exact timing of symptom onset relative to vaccination (immediate vs. hours vs. days). 1
• Prior tetanus-containing vaccine history and timing (increased Arthus risk if <2-5 years). 1
• Bilateral vs. unilateral symptoms (bilateral suggests systemic process like GBS). 1
• Nature of "tired arms" (true weakness vs. pain-limited movement vs. fatigue). 1
• Characteristics of discoloration (erythema vs. cyanosis vs. pallor vs. hemorrhagic). 1
• Associated symptoms: fever, headache, visual changes, decreased fetal movement. 3, 6

Physical Examination Priorities

• Measure bilateral arm circumferences to quantify swelling. 1
• Assess injection site for severe erythema, induration, warmth, or necrosis (Arthus reaction). 1
• Perform detailed neurologic examination including motor strength testing, reflexes, and sensory examination. 1
• Evaluate for compartment syndrome: severe pain with passive stretch, tense compartments, paresthesias. 1
• Check blood pressure and assess for preeclampsia signs (proteinuria, hyperreflexia, right upper quadrant pain). 6
• Assess hand perfusion: capillary refill, pulses, temperature. 5

Diagnostic Testing

• If true motor weakness is present, obtain urgent neurology consultation and consider nerve conduction studies/EMG for brachial neuritis or GBS. 1, 2
• If DVT suspected, obtain upper extremity venous duplex ultrasound. 5
• If compartment syndrome suspected, measure compartment pressures emergently. 1
• Basic labs: CBC (thrombocytopenia), comprehensive metabolic panel, urinalysis (proteinuria for preeclampsia). 6

Management Based on Diagnosis

For Typical Local Reaction or Extensive Limb Swelling

• Reassure that this is expected and will resolve within 4-7 days. 1, 3
• Symptomatic management: ice, elevation, acetaminophen for pain. 3
• Close follow-up to ensure resolution. 3

For Arthus Reaction

• Symptomatic management as above. 1
• Document that patient should not receive tetanus toxoid-containing vaccines more frequently than every 10 years, even for wound management. 1
• Typically resolves without sequelae. 1

For Brachial Neuritis

• Neurology consultation for confirmation. 2
• Usually self-limited but may require physical therapy. 1
• Not a contraindication to future tetanus-containing vaccines. 1

For GBS

• Immediate hospitalization for monitoring of respiratory function and autonomic instability. 1
• Neurology consultation for IVIG or plasmapheresis consideration. 1
• History of GBS within 6 weeks of tetanus toxoid is a precaution for future doses. 1, 2

Critical Pitfalls to Avoid

• Do not dismiss bilateral arm weakness as simple soreness without formal strength testing—this could be early GBS. 1
• Do not assume all post-vaccine symptoms are benign—pregnancy complications like preeclampsia can coincidentally occur. 6
• Do not forget to assess fetal well-being with non-stress test given maternal symptoms at 35 weeks. 6
• Do not fail to document severe reactions in the medical record and report to VAERS. 7, 3
• Remember that while Tdap is safe in pregnancy with no increased serious adverse events in large studies, individual severe reactions can still occur. 1, 3, 5, 6