What could be the cause of a patient experiencing severe restlessness and paresthesia in her legs, particularly after being on her feet all day?

Restless Legs Syndrome (RLS) is the Most Likely Diagnosis

This patient's symptoms of feeling like "crawling out of her own skin" with very restless legs strongly suggest Restless Legs Syndrome (RLS), a neurological sensorimotor disorder that requires systematic evaluation and treatment. 1, 2

Diagnostic Confirmation

To confirm RLS, assess whether the patient meets all five essential diagnostic criteria 1:

1. Urge to move the legs - Usually accompanied by uncomfortable or unpleasant sensations (the "crawling" sensation she describes) 1
2. Worsening with rest - Symptoms begin or worsen during periods of inactivity, such as sitting or lying down after being on her feet all day 1
3. Relief with movement - Symptoms are partially or totally relieved by walking or stretching, at least as long as the activity continues 1
4. Circadian pattern - Symptoms occur or worsen in the evening or night compared to daytime 1
5. Not explained by another condition - Must rule out mimics including leg cramps, venous stasis, leg edema, arthritis, positional discomfort, peripheral neuropathy, or vascular disease 1

Critical Differential Diagnosis Considerations

Important pitfall: Several conditions can superficially meet RLS criteria but are distinct entities 1:

• Venous stasis - Particularly relevant given she is on her feet all day; look for visible varicosities, edema, and skin changes 1
• Peripheral neuropathy - Perform thorough neurological examination to identify sensory deficits or radiculopathy 1
• Vascular disease/intermittent claudication - Assess for pain with walking that improves with rest (opposite pattern from RLS) 1
• Arthritis - Joint-specific pain patterns 1
• Positional discomfort or muscle aches - From prolonged standing 1

Essential Laboratory Evaluation

Check serum ferritin immediately - This is the single most important laboratory test 1, 3:

• Ferritin levels less than 50 ng/mL are consistent with RLS diagnosis and indicate need for iron supplementation 1
• Iron deficiency is a critical secondary cause and treating it may improve symptoms and reduce risk of treatment complications 3, 4
• The American Geriatrics Society states that impaired dopamine transport in the substantia nigra due to reduced intracellular iron plays a critical role in RLS pathophysiology 1, 3

Underlying Causes to Consider

Primary (Idiopathic) RLS

• Strong genetic component with familial clustering 1, 3
• First and second-degree relatives have significantly increased risk 1, 3

Secondary RLS - Key Associations 1, 3

• Iron deficiency anemia
• End-stage renal disease
• Pregnancy
• Medications that can exacerbate symptoms: tricyclic antidepressants, SSRIs, lithium, dopamine antagonists (antipsychotics) 1, 3

Lifestyle Risk Factors 1, 3

• Increased BMI
• Caffeine intake
• Sedentary lifestyle (though she is on her feet all day, this may worsen symptoms paradoxically)
• Tobacco use

Treatment Algorithm

If Ferritin < 50 ng/mL

Start with iron supplementation 1, 4

If Pharmacologic Treatment is Required

First-line: Dopamine receptor agonists 1, 4:

• 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; titrate weekly by 0.5 mg increments to maximum 4 mg 1
• Pramipexole: Start 0.125 mg orally 2-3 hours before bedtime; double every 4-7 days to maximum 0.5 mg 1

Critical warning about dopamine agonists 1, 5:

• Monitor for orthostatic hypotension, especially important in older patients 1
• Watch for compulsive behaviors (gambling, increased sexual urges, uncontrolled spending, binge eating) 5
• Risk of augmentation - paradoxical worsening with earlier symptom onset, increased intensity, or spread to other body parts 1, 5

Second-line alternatives 1, 4:

• Gabapentin or pregabalin - Particularly useful if augmentation develops or to avoid dopaminergic side effects 4, 6
• Opioids (tramadol, oxycodone) - For severe cases or augmentation 4, 6

Key Clinical Pitfalls to Avoid

• Do not miss iron deficiency - Check ferritin even if hemoglobin is normal 1, 3
• Do not overlook venous stasis - Her occupational history of prolonged standing makes this a critical mimic to exclude 1
• Do not use levodopa-carbidopa - Higher augmentation rates compared to newer dopamine agonists 1
• Do not abruptly discontinue dopaminergic therapy - Taper to avoid withdrawal-emergent hyperpyrexia and confusion 5
• Do not ignore medication review - Many common medications worsen RLS 1, 3