Burning Pain in Legs Worse in the Morning
The most likely diagnosis is Restless Legs Syndrome (RLS), which characteristically presents with burning sensations in the legs that worsen during rest periods (including overnight) and improve with movement. 1, 2
Key Diagnostic Features of RLS
RLS must meet all five essential diagnostic criteria 1:
- Urge to move the legs accompanied by uncomfortable or unpleasant sensations (often described as "burning" or "crawling") 1, 3
- Symptoms begin or worsen during rest (sitting, lying down, or overnight periods) 1, 4
- Relief with movement such as walking or stretching, lasting as long as the activity continues 1, 4
- Circadian pattern with symptoms occurring or worsening in the evening/night compared to daytime 1, 4
- Not better explained by another condition 1, 2
Painful, burning RLS is a recognized severe subtype, affecting 55-61% of RLS patients, and represents a more severe disease variant with higher symptom burden. 5
Critical Differential Diagnoses to Exclude
Peripheral Neuropathy (Especially Diabetic)
- Presents with burning pain but typically lacks the circadian pattern and relief with movement that defines RLS 6, 2
- Associated with additional sensory changes, numbness, or tingling 6
- Check HbA1c, thyroid function, and perform neurological examination 7
Venous Stasis
- Critical mimic to exclude, particularly with history of prolonged standing 1, 2
- Presents with tight, bursting pain and visible edema/venous changes 6
- Lacks the characteristic relief with movement seen in RLS 1
Nocturnal Leg Cramps
- Differentiated by asking: "What does it feel like?" 7
- Cramps are sudden, painful muscle contractions (not burning dysesthesias) 7
- Do not have the urge to move or circadian worsening pattern of RLS 6, 7
Peripheral Arterial Disease (PAD)
- Burning pain with exercise (claudication) that improves with rest—opposite pattern from RLS 6
- Check lower extremity pulses and consider ankle-brachial index if vascular disease suspected 6
Essential Laboratory Evaluation
Check serum ferritin immediately as iron deficiency is the most critical secondary cause of RLS 1, 3:
- Ferritin <50 ng/mL indicates iron deficiency associated with RLS, even if hemoglobin is normal 1, 3
- This is treatable and must not be missed 1
Additional testing if secondary causes suspected 7:
Treatment Algorithm
First-Line: Iron Supplementation (if ferritin <50 ng/mL)
Start iron supplementation immediately if ferritin is low, as this addresses the underlying pathophysiology 1, 3
First-Line: Dopamine Agonists (for moderate-severe symptoms)
Ropinirole 1:
- 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
- Weekly titration by 0.5 mg increments to maximum 4 mg
Pramipexole 1:
- Start 0.125 mg orally 2-3 hours before bedtime
- Double every 4-7 days to maximum 0.5 mg
Alternative First-Line: Gabapentinoids
Pregabalin is FDA-approved for neuropathic pain and can be effective for RLS 8, 3:
- Consider if dopamine agonists are contraindicated or not tolerated
- Particularly useful if painful, burning component is prominent 3, 5
Critical Pitfalls to Avoid
Do not miss iron deficiency even with normal hemoglobin—check ferritin in all RLS patients 1
Do not use levodopa-carbidopa as first-line therapy despite it being mentioned in older literature—it causes augmentation (worsening of symptoms) 1, 4
Review all medications that can worsen RLS 7:
- Diuretics
- Calcium channel blockers
- Lithium
- NSAIDs
Perform thorough neurological examination to identify mimics like peripheral neuropathy, radiculopathy, or arthritis that present with leg discomfort 1, 2
Do not abruptly discontinue dopaminergic therapy once started, as this can cause rebound worsening 1