RLS (Willis–Ekbom disease) is a clinical diagnosis, but its single most important modifiable driver is brain iron deficiency, which can exist even with a "normal" ferritin. Guidelines recommend treating to a serum ferritin above 75 µg/L (and transferrin saturation above 20%). Crucially, the ferritin check is also a safety net: finding genuine iron-deficiency anaemia mandates a search for a cause, and in adults that means actively excluding gastrointestinal malignancy under NICE NG12 — RLS is the presenting symptom, but the occult colorectal or gastric cancer is the diagnosis you must not miss.

The mnemonic URGE captures the four essential diagnostic criteria — all must be present. The circadian element (evening/night worsening) is the most discriminating feature and reflects the underlying dopaminergic and iron pathophysiology, which follows a daily rhythm. Asking specifically "is it worse when you sit still in the evening, and does getting up and walking ease it?" rapidly separates RLS from nocturnal cramps (sudden painful muscle contraction, no urge), positional discomfort, and akathisia (constant, drug-related, not circadian).

The most common misdiagnosis is conflating RLS with nocturnal leg cramps — they are managed completely differently. Cramps are a painful, visible, palpable muscle contraction relieved by passively stretching the muscle; RLS is an urge to move with an unpleasant (but usually not "painful") deep sensation relieved by voluntary movement. The other clinically vital distinction is claudication, because it is relieved by rest and worsened by exercise — exactly opposite to RLS — and it signals arterial disease needing vascular assessment.

Ferritin is the investigation that changes management. Even when it is within the laboratory "normal" range, a level below 75 µg/L warrants iron replacement in symptomatic RLS, because the relevant deficiency is in the brain, not necessarily the blood. Transferrin saturation below 20% supports the case for treatment, including intravenous iron. Always interpret ferritin against CRP, since infection or inflammation can elevate it spuriously and mask functional iron deficiency.

Most RLS is managed entirely in primary care. The two situations that genuinely need specialist input are augmentation (a paradoxical drug-induced worsening that requires careful agent switching, usually under neurology) and refractory disease where combination therapy or IV iron is being considered. The non-negotiable referral, however, is the patient with unexplained iron-deficiency anaemia, who enters the NG12 cancer pathway regardless of how typical their leg symptoms appear.

The treatment paradigm has shifted: alpha-2-delta ligands (gabapentin, pregabalin) are now favoured first-line ahead of dopamine agonists because dopamine agonists, although initially very effective, frequently cause augmentation over months to years and carry a real risk of impulse-control disorders that patients will not volunteer unless asked. The foundation beneath any drug, though, is iron repletion and removal of pharmacological triggers — a substantial proportion of patients improve with these alone and need no ongoing RLS-specific medication.

Augmentation is the single most important iatrogenic complication of RLS treatment and the reason guidelines have demoted dopamine agonists. The tell-tale features are temporal (symptoms creeping earlier into the afternoon), spatial (spreading to the arms), and pharmacodynamic (each dose helps for less time). The instinct to raise the dose accelerates the problem. Correct management is iron optimisation and a planned cross-taper to an alpha-2-delta ligand, anticipating a rebound flare during withdrawal.

Non-pharmacological measures are not a token gesture in RLS — for mild and intermittent disease they are often sufficient, and for everyone they reduce the dose and number of drugs required. The highest-yield changes are eliminating evening caffeine, alcohol and nicotine, auditing the medication list for hidden dopamine antagonists and sedating antihistamines, and using movement, stretching and temperature manoeuvres at symptom onset. Mental alerting during enforced rest exploits the same arousal pathways that movement does.

Follow-up in RLS has two jobs: confirming that iron repletion has been achieved and maintained, and vigilantly screening for augmentation and impulse-control disorders in anyone on a dopamine agonist. The safety-net never closes on the iron-deficiency question — if anaemia was present and unexplained, the GI cancer pathway must be completed, and recurrent or refractory deficiency should prompt you to revisit it. Any drift towards unilateral, painful, or neurologically abnormal symptoms means the diagnosis is no longer simple RLS.