What is the cause and treatment for an adult patient with itchy feet and hands, especially at night, without any visible rash or lesions?

Itchy Hands and Feet at Night Without Rash: Diagnosis and Management

The most critical diagnosis to rule out immediately is intrahepatic cholestasis, particularly if the patient is pregnant, as this condition poses significant fetal risk including stillbirth; in non-pregnant adults, systemic causes including chronic kidney disease, liver disease, hematologic disorders, and iron metabolism abnormalities must be systematically excluded before considering neuropathic or psychogenic etiologies. 1, 2

Immediate Diagnostic Priorities

Key Clinical Features to Assess

The pattern you describe—palmar and plantar pruritus that worsens at night without visible rash—is the hallmark presentation of intrahepatic cholestasis of pregnancy (ICP) if the patient is pregnant, or suggests systemic disease in non-pregnant adults. 1

Critical history elements to obtain:

• Pregnancy status (ICP typically presents in second/third trimester) 1
• Timing of symptom onset (sudden vs. gradual) 1, 2
• Presence of dark urine or jaundice (suggests hepatobiliary disease beyond simple ICP) 1
• Medication history, particularly opioids and hydrochlorothiazide (common drug-induced causes) 1
• Aquagenic symptoms (itching triggered by water contact suggests polycythemia vera) 1
• Constitutional symptoms: weight loss, fevers, night sweats (suggests lymphoma) 1
• Renal or liver disease history 1, 3

First-Line Laboratory Workup

Order immediately:

• Serum bile acids (most sensitive test for cholestasis; elevated >10 μmol/L is diagnostic for ICP) 1
• Complete blood count with differential (evaluate for polycythemia, eosinophilia, lymphoma) 1, 4, 5
• Comprehensive metabolic panel including creatinine, BUN, liver function tests 4, 3, 5
• Ferritin and iron studies (both iron deficiency and iron overload cause pruritus) 1
• Fasting glucose or HbA1c 4, 5
• Thyroid-stimulating hormone 4, 3, 5

Second-tier testing if initial workup unrevealing:

• JAK2 V617F mutation if polycythemia suspected (present in 97% of polycythemia vera cases) 1
• Erythrocyte sedimentation rate, lactate dehydrogenase (if hematologic malignancy suspected) 1, 5
• HIV screening, hepatitis serologies 4, 3
• Chest radiography (for occult malignancy in patients >60 years) 1, 3, 5

Common Diagnostic Pitfalls

Do not dismiss this symptom as benign. Pruritus without rash (generalized pruritus without overt rash, or GPWOR) represents systemic disease in a substantial proportion of cases, and haematological causes account for approximately 2% of cases. 1

Excoriations from scratching may be mistaken for primary rash—the key is identifying whether lesions are primary (indicating skin disease) or secondary to scratching. 1, 4

In patients over 60 years with diffuse itch <12 months duration, maintain high suspicion for underlying malignancy, particularly with concurrent liver disease. 5

Specific Disease Considerations

If Pregnant: Intrahepatic Cholestasis of Pregnancy

• Poses minimal maternal risk but significant fetal risk (preterm delivery, stillbirth) 1
• Treatment: Ursodeoxycholic acid is standard therapy; delivery timing should be coordinated with maternal-fetal medicine 1
• Pruritus resolves after delivery in most cases 1

If Polycythemia Vera Suspected

• Aquagenic pruritus is pathognomonic (intense itching after water contact without skin lesions) 1
• Associated findings: elevated hemoglobin/hematocrit, microcytosis (from secondary iron deficiency), elevated WBC or platelets, low ESR 1
• Treatment: Ruxolitinib (JAK1/JAK2 inhibitor) produces rapid reduction in pruritus scores 1
• Aspirin 300 mg daily has shown efficacy for pruritus relief 1

If Chronic Kidney Disease

• Uremic pruritus is common in dialysis patients 3, 2
• Evaluate BUN and creatinine levels 4, 3

If Iron Deficiency

• Check ferritin; if <15-25 μg/L or unexplained anemia/microcytosis present, evaluate for celiac disease with tissue transglutaminase antibodies (if not gluten-free for ≥6 weeks) 1
• Iron overload (hemochromatosis or hyperferritinemia) also causes pruritus 1

Symptomatic Management While Investigating

Initiate immediately regardless of underlying cause:

Skin Barrier Restoration

• Apply emollients liberally at least once daily to entire body, not just symptomatic areas 6, 7, 4
• Use urea 10% cream or glycerin-based moisturizers 1, 6, 7
• Avoid hot water and excessive soap use (use lukewarm water and soap substitutes) 1, 6

Nighttime-Specific Interventions

• Apply moisturizer followed by cotton gloves and socks at night to create occlusive barrier 1
• Consider topical polidocanol cream for itch relief 6
• Oral sedating antihistamines at bedtime may provide symptomatic relief through sedation, though evidence for direct antipruritic effect is limited 6, 7, 4

Topical Therapy

• Low-potency topical corticosteroid (hydrocortisone 1-2.5%) can be applied to hands and feet if no contraindication 1, 6, 7
• Avoid alcohol-based preparations 1

What NOT to Do

• Do not use non-sedating antihistamines—they have minimal to no value for pruritus not mediated by histamine 6, 7
• Do not delay investigation while treating symptomatically 1, 3

When to Refer

Refer to dermatology if:

• Diagnosis remains unclear after initial workup 6, 4
• Symptoms persist despite treatment of underlying cause 1
• Skin biopsy needed to exclude cutaneous lymphoma (rare but possible with normal-appearing skin) 1

Refer to hematology/oncology if:

• Abnormal blood counts or concerning for malignancy 1
• Confirmed polycythemia vera or lymphoma 1

Refer to hepatology if:

• Elevated bile acids or liver enzymes 1
• Suspected chronic liver disease 2

Refer to maternal-fetal medicine if:

• Pregnant with confirmed or suspected ICP 1