What are the differential diagnoses and treatment options for a patient presenting with diffuse warts on the hands, likely caused by Human Papillomavirus (HPV)?

Differential Diagnoses for Diffuse Warts on Hands

The primary differential diagnoses for diffuse warts on the hands include common warts (verruca vulgaris), flat warts (verruca plana), corns, calluses, and actinic keratoses, with the definitive diagnostic test being paring down the lesion with a scalpel to reveal pinpoint bleeding (pathognomonic for warts) versus a translucent core (corns) or homogenous keratin (calluses). 1

Key Diagnostic Features to Distinguish Lesions

Common Warts (Verruca Vulgaris)

• Caused by HPV types 1,2,4,27, and 57, with HPV-1 and HPV-2 being most common 2
• Appear as hyperkeratotic papulonodules with disrupted or absent skin lines across the lesion 1
• Paring reveals pinpoint bleeding from exposed capillary loops of elongated dermal papillae—this is pathognomonic 2, 1
• May present as filiform warts, flat warts, or mosaic warts depending on morphology 3
• Develop following HPV infection of keratinocytes at the basal layer, resulting in epidermal thickening and hyperkeratinization 2

Corns (Heloma Durum)

• Paring reveals a translucent central core without bleeding 1
• Preserved skin lines may be visible 1
• Occur at pressure points, typically on feet but can occur on hands with repetitive trauma 1

Calluses (Tyloma)

• Characterized by diffuse, yellowish thickening at pressure areas 1
• Paring shows homogenous thickened keratin without bleeding 1
• Skin lines remain intact 1

Actinic Keratoses

• Occur on chronically sun-exposed skin such as dorsa of hands 4
• Present as discrete patches of erythema and scaling, typically in middle-aged and elderly individuals 4
• Show epithelial dysplasia histologically, not koilocytes characteristic of HPV lesions 4
• Primary cause is chronic UV radiation exposure, not HPV infection 4

Diagnostic Approach

Physical Examination Technique

• Soak the lesion in warm water to soften tissue before examination 1
• Pare down carefully with a scalpel blade, removing superficial layers 1
• Inspect closely for bleeding points (wart) versus translucent core (corn) versus uniform opacity (callus) 1
• Assess for disrupted skin lines (warts) versus preserved lines (corns/calluses) 1

Special Considerations for Diffuse Hand Warts

• Multiple or extensive warts in adults may warrant consideration of underlying immune deficiency 2
• Immunocompromised patients (HIV, organ transplant recipients, those on immunosuppressive therapy) are at higher risk for severe and persistent warts 5
• Atypical lesions, unresponsive lesions, or lesions in immunocompromised individuals may require biopsy 6

Treatment Options

First-Line Treatments

• Salicylic acid 15-40% topical paints or ointments are recommended as first-line treatment (Level of evidence 1+, Strength A) 1
• Cryotherapy with liquid nitrogen applied fortnightly for 3-4 months 7, 1
• Expectant management is entirely acceptable for immunocompetent patients with asymptomatic warts, as 50% clear spontaneously within 1 year in children and two-thirds by 2 years 2, 1

Second-Line Options

• Imiquimod cream is FDA-approved for external genital warts but not specifically for hand warts 8
• Trichloroacetic acid (TCA) 80-90% applied weekly to warts, powdered with talc or sodium bicarbonate to remove unreacted acid 7
• Electrodesiccation or electrocautery for refractory lesions 7

Refractory Cases

• Intralesional immunotherapy with purified protein derivative (PPD) has shown complete clearance in immunocompromised patients with multiple recalcitrant hand warts within 6 weeks 5
• Carbon dioxide laser or surgical excision for extensive warts unresponsive to other regimens 7
• Topical cidofovir may be considered as an alternative for refractory cases, particularly in HIV-infected patients 9

Critical Pitfalls to Avoid

• Never use destructive treatments on facial warts without extreme caution due to scarring risk 1
• Avoid overdebridement of any lesion, which can cause pain and tissue damage 1
• Recognize that wart treatments do not eradicate HPV infection—recurrence is common (usually at least 25% within 3 months with all modalities) 7, 1
• Do not use chemical corn removers or plasters on diabetic patients due to high complication risk 1
• HPV can spread through direct contact or via the environment and may remain infectious outside the body for months or years 2
• Treatment should be guided by anatomic site, size, number of warts, expense, efficacy, convenience, and potential adverse effects 7