What could be causing tingling and crawling sensations in both lower legs, back, and arms, along with a red, swollen face, and how should it be treated?

Evaluation and Management of Tingling, Crawling Sensations in Limbs with Facial Swelling

This symptom constellation requires immediate evaluation to exclude life-threatening conditions, particularly drug-induced toxicity, severe infections, or angioedema, before considering benign neurological causes.

Immediate Life-Threatening Exclusions

Drug-Induced Toxicity (If on Chemotherapy)

• If the patient is receiving chemotherapy agents (5-fluorouracil, capecitabine, doxorubicin, sorafenib, cabozantinib, sunitinib, or regorafenib), suspect hand-foot syndrome (HFS) or hand-foot skin reaction (HFSR), which presents with tingling and dysesthesia of extremities progressing to burning pain, swelling, and erythema 1.
• HFS typically develops within days to weeks after chemotherapy initiation, with first symptoms being dysesthesia and tingling in palms and soles 1.
• The red, swollen face may represent concurrent dermatological toxicity from EGFR inhibitors, MEK inhibitors, or mTOR inhibitors, which cause papulopustular eruptions with erythema and swelling 1.
• Initiate oral antibiotics (doxycycline 100 mg twice daily OR minocycline 50 mg twice daily) for 6 weeks AND topical moderate-potency corticosteroids if grade 1-2 facial toxicity is present 1.

Severe Infection

• Exclude erysipelas or cellulitis if the facial swelling is accompanied by fever, as these skin infections can present with rapidly spreading edema, redness, and heat 1, 2.
• Blood cultures are positive in only 5% of cellulitis cases, but systemic manifestations including fever, tachycardia, confusion, and hypotension may precede skin abnormalities 1.
• Necrotizing fasciitis must be considered if there is widespread petechiae, ecchymoses, and systemic toxicity 1.

Angioedema

• A red, swollen face with tingling sensations could represent angioedema (mast cell-driven or bradykinin-mediated), which can progress to life-threatening laryngeal involvement 1, 2.
• Hereditary angioedema (HAE) presents with discrete episodes of nonpruritic, nonpitting swelling involving extremities, face, and oropharynx, with prodromal symptoms including localized tingling or erythema marginatum 1.
• Laryngeal angioedema carries a 30% or higher mortality rate if untreated, requiring immediate treatment with plasma-derived C1 inhibitor, icatibant, or ecallantide 1.
• ACE inhibitors should be avoided as they decrease bradykinin catabolism and can precipitate attacks 1.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

• DRESS syndrome presents with facial erythema and swelling accompanied by systemic symptoms, representing a severe adverse drug reaction that requires immediate recognition 2.

Neurological Causes (If Life-Threatening Excluded)

Peripheral Neuropathy

• Painful diabetic peripheral neuropathy (DPN) commonly presents with burning pain, electrical shock-type shooting pain, uncomfortable tingling (paresthesia), and crawling sensations (formication) in lower legs that may progress upward 1.
• Patients describe symptoms as "walking barefoot on marbles" or "walking barefoot on hot sand," with subjective sensations of altered temperature perceptions 1.
• Symptoms are characteristically more severe at night, resulting in sleep disturbance and profound depression in up to two-thirds of patients 1.
• However, DPN does not explain the red, swollen face, requiring consideration of concurrent conditions 1.

Restless Leg Syndrome

• Restless leg syndrome presents with crawling, tingling, or aching sensations in limbs creating an urge to move, affecting 3-15% of the population 3.
• This can be secondary to medications, iron deficiency, or neuropathies 3.
• Treatment with rotigotine patch (dopamine agonist) or gabapentin enacarbil is indicated if symptoms cause functional disability 3.

Neurocutaneous Dysesthesias

• Dysesthesia encompasses pruritus, burning, tingling, crawling, or cold sensations without primary cutaneous findings, often caused by nerve trauma, impingement, or irritation 4.
• Specific syndromes include notalgia paresthetica (back), meralgia paresthetica (thighs), and brachioradial pruritus (arms) 4.
• These conditions are of neurologic origin with dermatologic consequences but do not explain facial swelling 4.

Diagnostic Algorithm

1. Obtain medication history immediately, specifically chemotherapy agents, ACE inhibitors, and recent drug initiations 1.
2. Assess for fever, mucosal involvement, systemic symptoms (malaise, confusion, hypotension) to exclude infection or severe drug reactions 1, 2.
3. Examine for Nikolsky sign (skin shearing with minimal trauma), purpuric macules, or flaccid bullae suggesting Stevens-Johnson syndrome/toxic epidermal necrolysis 2.
4. Measure temperature difference between affected and unaffected limbs if Charcot neuro-osteoarthropathy is suspected in diabetic patients with neuropathy 1.
5. Evaluate for diabetes mellitus with HbA1c and assess for peripheral neuropathy if neurological symptoms predominate without other findings 1.

Treatment Approach

If Chemotherapy-Related

• Continue drug at current dose for grade 1-2 toxicity; initiate oral antibiotics for 6 weeks with topical corticosteroids 1.
• Interrupt treatment for grade ≥3 toxicity until severity decreases to grade 0-1; add systemic corticosteroids (prednisone 0.5-1 mg/kg for 7 days) 1.

If Angioedema

• Administer plasma-derived C1 inhibitor, icatibant, or ecallantide immediately for acute attacks 1.
• Discontinue ACE inhibitors permanently 1.

If Infection

• Initiate appropriate antibiotics based on culture results; blood cultures have low yield (5%) but should be obtained 1.

If Neuropathy

• Optimize glycemic control gradually (avoid HbA1c drops >3% in short periods to prevent treatment-induced neuropathy) 1.
• Prescribe tricyclic antidepressants, SNRIs, or gabapentinoids for painful symptoms 1.

Critical Pitfalls to Avoid

• Never dismiss a red, swollen face as simple dermatitis without excluding angioedema, as laryngeal involvement can be fatal 1, 2.
• Do not delay treatment for suspected severe infections or drug reactions while awaiting diagnostic confirmation 1, 2.
• Avoid rapid glycemic reduction in diabetic patients with long-standing hyperglycemia, as HbA1c drops >3% can paradoxically worsen neuropathy 1.
• Do not assume all tingling sensations are benign neuropathy—chemotherapy-induced HFS requires dose modification 1.