What is the differential diagnosis for a patient with extreme pruritus (itching) in random areas of the body, leading to a stinging sensation and involuntary limb movement for relief, particularly when trying to fall asleep?

Differential Diagnosis for Extreme Itching with Stinging and Involuntary Limb Movement at Night

The most likely diagnosis is restless leg syndrome (RLS) secondary to nocturnal pruritus, with atopic dermatitis, polycythemia vera, and neuropathic pruritus as the primary differential considerations. 1

Primary Diagnostic Considerations

Restless Leg Syndrome Secondary to Itch

• Many children and adults with severe pruritus develop a comorbid diagnosis of restless leg syndrome, which appears secondary to itch-induced movements 1
• RLS is diagnosed clinically as an unrelenting urge at night and before sleep onset to move the legs, which matches your patient's presentation 1
• The key distinguishing feature is that the movement provides temporary relief, and symptoms are worse when trying to fall asleep 1
• This can also present as periodic leg movement disorder, defined by repetitive limb movements that occur only during sleep, not before sleep onset 1

Atopic Dermatitis (AD)

• AD commonly presents with extreme nocturnal pruritus that disrupts sleep, with scratching highest during transitional sleep stages (N1 and N2) 1
• Patients experience frequent nighttime awakenings and greater difficulty falling asleep 1
• The "random areas" description fits with AD's variable distribution pattern 1
• Sleep disturbance in AD is greatest during the first half of the night, resulting in decreased NREM sleep 1

Polycythemia Vera (PV)

• Generalized pruritus occurs in approximately 48% of PV patients and is often the most agonizing symptom, causing sleep deprivation 1
• The pruritus is characteristically exacerbated by hot water (aquagenic pruritus) 1
• PV-associated pruritus can result in interference with sleep and physical activities 1
• This should be strongly considered if the patient has microcytosis, raised white cell or platelet count, and low ESR 1

Neuropathic Pruritus

• Neuropathic itch causes sensory symptoms including burning, stinging, and tingling—matching the "stinging" sensation described 1, 2
• Small fiber neuropathy can cause generalized pruritus and may be associated with diabetes, HIV, or sarcoidosis 1
• The stinging quality before movement is highly characteristic of neuropathic involvement 2
• Neuropathic itch shares clinical features with neuropathic pain and often presents with hypersensitization to stimuli 3, 2

Essential Initial Workup

Laboratory Investigations (Order All)

• Complete blood count with differential and blood film to screen for polycythemia vera, lymphoma, and eosinophilia 1, 4
• Ferritin level as iron deficiency causes pruritus in 25% of patients with systemic disease 1, 4
• Liver function tests to evaluate for cholestatic causes 1, 4
• Renal function tests (urea and electrolytes) to assess for uremic pruritus 1, 4
• Fasting glucose or A1C to screen for diabetes-related neuropathy 5
• Thyroid-stimulating hormone as part of comprehensive endocrine screening 5

If Polycythemia Vera is Suspected

• Check for JAK2 mutation if hemoglobin/hematocrit is elevated, especially with microcytosis, raised platelet count, and low ESR 1
• Measure serum erythropoietin level if JAK2 is negative 1

If Neuropathic Pruritus is Suspected

• Consider skin biopsy to confirm small fiber neuropathy, though this may not show changes on routine examination 1
• Detailed neurological examination is indicated only if clinically suggested 1

Immediate Symptomatic Management

First-Line Treatment

• Liberal application of high lipid-content emollients to all affected areas, as this forms the foundation of pruritic treatment 6, 4, 5
• Non-sedating antihistamines during the day: loratadine 10 mg daily, cetirizine 10 mg daily, or fexofenadine 180 mg daily 6, 4
• Diphenhydramine 25-50 mg at bedtime specifically for nighttime pruritus interfering with sleep due to its sedative properties 6

Topical Therapy

• Hydrocortisone 1% cream applied 3-4 times daily to affected areas for inflammatory component 6
• Alternatively, triamcinolone 0.1% or mometasone 0.1% for more severe inflammation 4

Lifestyle Modifications

• Avoid hot showers and excessive soap use, which worsen xerosis 6
• Limit water exposure 5

Disease-Specific Treatment if Diagnosis Confirmed

If Polycythemia Vera

• Cytoreductive therapy, aspirin, interferon-α, SSRIs (particularly paroxetine with >80% response rate), PUVA, or UVB phototherapy 1
• Low-dose aspirin (81 mg/day) produces prompt relief within hours in most patients 1

If Neuropathic Pruritus

• Medications effective for neuropathic pain: gabapentin, carbamazepine, or pregabalin 1, 2
• These agents target the underlying neuronal pathology 3, 2

Critical Red Flags

• Development of facial swelling, difficulty breathing, or systemic symptoms requires emergency evaluation for anaphylaxis 6
• Enlarged lymph nodes or masses should prompt referral for excision or ultrasound-guided core biopsy to rule out lymphoma 1
• Weight loss, fevers, and night sweats suggest lymphoma 1

Reassessment Strategy

If symptoms fail to improve after 2 weeks of treatment, proceed with skin biopsy and specialist referral (dermatology for suspected dermatologic cause, hematology for suspected PV, neurology for suspected neuropathic cause) 6, 4