What could be causing my shaky legs, tingling in lower legs and arms, and facial flushing, and how should it be treated?

Evaluation of Shaky Legs, Tingling in Lower Legs and Arms, and Facial Flushing

Your symptoms require immediate evaluation to rule out anaphylaxis first, followed by systematic assessment for restless legs syndrome, peripheral neuropathy, and medication-induced causes, with facial flushing suggesting either carcinoid syndrome, pheochromocytoma, or alcohol-related acetaldehyde accumulation. 1

Immediate Life-Threatening Causes to Exclude

Anaphylaxis Assessment

• Check immediately for anaphylaxis criteria: acute onset with skin/mucosal involvement plus either respiratory compromise or reduced blood pressure, or two or more organ systems involved rapidly after allergen exposure 1
• If anaphylaxis is suspected, administer epinephrine 0.3 mg intramuscularly into the mid-outer thigh immediately—delayed epinephrine is associated with increased mortality and hypoxic-ischemic encephalopathy 1
• Obtain serum tryptase levels 15 minutes to 3 hours after symptom onset and plasma histamine within 5-60 minutes, though normal levels do NOT rule out anaphylaxis 1

Systematic Evaluation for Shaky Legs and Tingling

Restless Legs Syndrome (RLS) Evaluation

Assess using the four essential diagnostic criteria: 2

1. Is there an urge to move the legs accompanied by uncomfortable or unpleasant sensations? 2
2. Do symptoms begin or worsen during rest or inactivity (sitting/lying down)? 2
3. Are symptoms partially or totally relieved by movement (walking/stretching) for as long as activity continues? 2
4. Do symptoms worsen or only occur in the evening or night? 2

• Perform thorough neurologic examination to exclude peripheral neuropathy or radiculopathy as secondary causes 2
• Obtain serum ferritin—values less than 50 ng/mL are consistent with RLS diagnosis and suggest need for iron supplementation 2
• Consider that impairment of dopamine transport in the substantia nigra due to reduced intracellular iron plays a critical role in most RLS patients 2

Peripheral Neuropathy Assessment

Look for specific clinical patterns: 2

• Distal, symmetric sensory or sensorimotor polyneuropathy with sensory loss, paresthesias, numbness, cramps, burning feet, and tingling 2
• Small fiber sensory polyneuropathy (less frequently large fiber sensory neuropathy) 2
• Asymmetrical sensory/motor impairment suggesting mononeuritis 2

Perform electromyography with peripheral nerve neurophysiological tests to confirm peripheral nerve involvement 2

Orthostatic Tremor/Myoclonus Consideration

• Suspect in patients reporting unsteadiness with prolonged standing who exhibit cautious, wide-based gaits 3
• Surface electromyography (SEMG) is necessary to verify diagnosis—frequency ranges vary (2.6-15 Hz) 4
• Classical orthostatic tremor responds best to clonazepam, while orthostatic myoclonus responds to levetiracetam 3

Facial Flushing Evaluation

Critical Endocrine/Neoplastic Causes to Exclude

Measure the following immediately: 5

• Serum serotonin and urinary 5-hydroxyindoleacetic acid for carcinoid syndrome 5
• Plasma-free metanephrine and urinary vanillylmandelic acid for pheochromocytoma 5
• Consider gastrointestinal and thyroid tumors 5

Alcohol-Related Flushing (ALDH2 Deficiency)

• ALDH2*2 genetic variant produces inactive aldehyde dehydrogenase 2 enzyme, preventing normal metabolism of acetaldehyde into nontoxic acetic acid, causing systemic acetaldehyde accumulation with characteristic flushing, tachycardia, and reduced alcohol tolerance 5
• Screen for liver disease with AST/ALT (ratio >1.5), elevated GGT, elevated bilirubin, and macrocytic anemia 5
• Screen for alcohol use disorder using AUDIT-C ≥4 or AUDIT >8 5

Medication-Induced Flushing

Consider niacin, nicotine, catecholamines, ACE inhibitors, and vancomycin as potential causes 5

Treatment Approach Based on Diagnosis

If RLS is Confirmed

First-line pharmacologic therapy: 2

• Ropinirole: Start 0.25 mg orally 1-3 hours before bedtime, increase to 0.5 mg after 2-3 days, then 1 mg after 7 days, with weekly 0.5 mg increments to maximum 4 mg at week 7 if needed 2
• Pramipexole: 0.125 mg orally 2-3 hours prior to bedtime, double dose every 4-7 days to maximum 0.5 mg 2
• These dopamine receptor agonists are associated with less rebound and symptom augmentation than levodopa-carbidopa 2
• Side effects include nausea, orthostatic hypotension, sleepiness, headache, and compulsive behaviors—particular consideration should be given to drug interactions and orthostasis risk in older patients 2

If Peripheral Neuropathy is Confirmed

Consider pregabalin for neuropathic pain: 6

• Common adverse reactions include dizziness (21-32%), somnolence (12-22%), peripheral edema (9%), weight gain (4-12%), blurred vision (4-10%), ataxia (3-15%), and thinking abnormal (2-8%) 6
• Patients should be counseled not to drive or operate complex machinery until they gauge whether pregabalin affects their mental, visual, or motor performance 6
• Avoid abrupt discontinuation 6

If Alcohol-Related Flushing (ALDH2 Deficiency)

Complete alcohol abstinence is the definitive management 5

Common Pitfalls to Avoid

• Do not delay epinephrine if anaphylaxis criteria are met while waiting for laboratory confirmation 1
• Do not rely solely on tryptase or histamine levels to rule out anaphylaxis 1
• Do not overlook medication-induced flushing, which is far more common than neoplastic causes 1, 5
• Do not diagnose Bell's palsy without thorough history and physical examination to exclude other causes of facial paralysis 2
• Do not assume RLS without checking serum ferritin—iron deficiency states are often associated with secondary RLS 2
• In older patients, particular consideration should be given to drug interactions and orthostatic hypotension risk when prescribing dopamine agonists 2