What are the differential diagnoses and management options for isolated pruritus of the palms and soles?

Itchy Palms and Soles: Differential Diagnosis and Management

Immediate Action: Rule Out Life-Threatening and Infectious Causes First

Before treating symptomatically, you must obtain serologic testing for syphilis (RPR/VDRL plus treponemal-specific tests) and complete blood count to exclude secondary syphilis and Rocky Mountain Spotted Fever, both of which classically present with palmoplantar involvement and carry significant morbidity if missed 1, 2.

Critical Red Flags Requiring Urgent Workup

• Secondary syphilis: Obtain RPR/VDRL and treponemal testing in all patients with symmetric palmoplantar pruritus, especially if accompanied by red-brown macules or systemic symptoms 1, 2
• Rocky Mountain Spotted Fever: Check CBC for thrombocytopenia and obtain tick exposure history; RMSF has 5-10% mortality if untreated and requires immediate doxycycline 2
• Bullous pemphigoid (dyshidrosiform variant): Consider in elderly patients (ages 61-94) with new-onset recurrent or treatment-resistant palmoplantar blisters; 77% progress to other body sites 3
• Iron deficiency: Check complete blood count and ferritin in all patients with chronic generalized pruritus without rash, as iron deficiency is the most common systemic cause (25% of cases) and responds rapidly to replacement 4

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Differential Diagnosis Based on Clinical Presentation

If Vesicles or Blisters Are Present

• Pompholyx (dyshidrotic eczema): Intensely pruritic vesicles embedded in thick stratum corneum on lateral fingers and palms, lasting 3 weeks per episode; strongly associated with atopy and hyperhidrosis 5, 6
• Palmoplantar pustulosis: Chronic inflammatory disease with pustules, erythema, and scaling; 65.5% have smoking history; histologically shows loss of granular layer and suprapapillary plate thinning 7
• Dyshidrosiform bullous pemphigoid: Hemorrhagic or purpuric blisters in elderly patients; requires skin biopsy with direct immunofluorescence showing linear IgG and C3 at basement membrane zone 3

If Scaly Plaques Without Vesicles

• Palmoplantar psoriasis: Well-demarcated plaques with silvery scale; may involve face/neck simultaneously; justifies systemic therapy regardless of body surface area due to disproportionate disability 1, 2
• Tinea manuum/pedis: Unilateral involvement more common; confirm with KOH preparation or fungal culture 6
• Contact dermatitis: Asymmetric distribution corresponding to allergen exposure; patch testing may be indicated 6, 3

If Pruritus Without Visible Primary Lesions

• Iron deficiency: Check ferritin; if below lower limit of reference range (15-25 μg/L) or if anemia/microcytosis present, trial iron replacement 4
• Systemic causes: Screen for hepatic disease (especially cholestasis), uremia, malignancy, thyroid disease, and HIV 4

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Treatment Algorithm

Step 1: Topical Therapy for Pompholyx or Eczematous Conditions

• Superpotent topical corticosteroids (clobetasol propionate 0.05% cream or ointment) applied twice daily under occlusion (plastic wrap, gloves, or socks overnight) for 8-12 weeks 1, 8
• Urea 10% cream three times daily, including after hand washing, for keratolytic and humectant effects 8
• "Soak and smear" technique: Soak hands/feet in plain water for 20 minutes, then immediately apply thick moisturizer 8
• Calcineurin inhibitors (tacrolimus, pimecrolimus) are effective alternatives to corticosteroids for pompholyx 6

Step 2: Phototherapy for Refractory Cases

• Soak PUVA (psoralen immersion followed by UVA exposure) 2-3 times weekly for several months; low risk of cutaneous malignancy on palms/soles 1, 6
• Narrowband UVB or 308-nm excimer laser for localized lesions 1
• High-dose UVA-1 irradiation is as effective as systemic photochemotherapy 6

Step 3: Systemic Therapy for Severe or Refractory Disease

Oral acitretin 25 mg daily is the first-line systemic agent for palmoplantar psoriasis and severe pompholyx, with substantial improvement expected within 2 months 1, 8, 2.

• Methotrexate 15-25 mg weekly: Requires monitoring for hepatotoxicity and bone marrow suppression 1, 2
• Cyclosporine 2.5-5 mg/kg daily: Limit to ≤1 year due to nephrotoxicity risk; requires regular renal function and blood pressure monitoring 1, 2
• Alitretinoin: Efficacy demonstrated in chronic hand dermatitis including pompholyx 6
• Intradermal botulinum toxin: Emerging treatment for recalcitrant cases, particularly when hyperhidrosis is a contributing factor 6

Step 4: Biologic Therapy for Refractory Palmoplantar Psoriasis

• IL-17 inhibitors, IL-12/23 inhibitors (ustekinumab), or IL-23 inhibitors are preferred over TNF-α inhibitors based on higher skin-clearance rates in head-to-head studies 1
• TNF-α inhibitors (adalimumab, infliximab): Effective but can paradoxically induce pustular psoriasis of palms/soles in 1-2% of patients 1, 2

Step 5: Treatment for Dyshidrosiform Bullous Pemphigoid

• Systemic corticosteroids (prednisone 0.5-1 mg/kg daily) with or without topical corticosteroids 3
• Dapsone or immunosuppressants (azathioprine, mycophenolate mofetil) as steroid-sparing agents 3

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Critical Pitfalls to Avoid

• Never assume simple dermatitis without excluding syphilis: Delayed diagnosis of secondary syphilis has significant public health and individual morbidity implications 1, 2
• Do not delay doxycycline if RMSF is suspected: 50% of deaths occur within 9 days; mortality increases dramatically with delayed treatment 8, 2
• Antihistamines are ineffective for pompholyx: This is not an allergic reaction; cetirizine and similar agents will not relieve pruritus 8
• Avoid systemic corticosteroids as monotherapy in psoriasis: Can trigger severe flares, including potentially life-threatening generalized pustular psoriasis 1, 2
• Monitor lipids with acitretin: Manage triglycerides with fibrates and cholesterol with statins, but never use both concurrently due to rhabdomyolysis risk 1
• Consider neurologic and psychiatric comorbidities: At least 9 patients with dyshidrosiform bullous pemphigoid had neurologic conditions or psychiatric disorders 3

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When to Refer

• Failure of 8-12 weeks of intensive topical therapy under occlusion 1, 8
• Need for systemic therapy (acitretin, methotrexate, cyclosporine, biologics) requires dermatology supervision 1, 8, 2
• Suspected bullous pemphigoid requiring skin biopsy with direct immunofluorescence 3
• Consideration of phototherapy or intradermal botulinum toxin 1, 6