What is the pathophysiology, symptoms, diagnosis, management, and differential diagnosis of verrucae (warts) in patients of all ages, particularly children and young adults?

Verrucae (Warts): Comprehensive Clinical Overview

Pathophysiology

Verrucae result from human papillomavirus (HPV) infection of keratinocytes in the basal layer of the epidermis, leading to clonal proliferation, epidermal thickening, and hyperkeratinization that manifests as a visible wart weeks to months after initial infection. 1

• Over 150 genotypically different HPV types exist, with common warts primarily caused by HPV types 1,2,4,27, or 57, while plane warts are caused by HPV types 3 or 10 1
• The virus spreads through direct contact or environmental surfaces, with potential infectivity persisting for months or possibly years outside the body 1
• Transmission is particularly common during childhood recreational activities, with autoinoculation being a frequent mechanism of spread 2, 3

Clinical Presentation and Symptoms

Verrucae typically present as asymptomatic, hyperkeratotic papulonodules with disrupted skin lines, most commonly affecting hands, feet, and periungual areas. 3, 4

Morphological Subtypes:

• Common warts (Verruca vulgaris): Well-circumscribed, hyperkeratotic lesions on hands, arms, and legs 1, 4
• Plantar warts (Verruca plantaris): Occur on soles of feet, may be painful with weight-bearing 1
• Plane warts (Verruca plana): Flat, smooth-surfaced lesions 1
• Periungual warts: Affect nail folds and can involve the nail bed 4

Key Clinical Features:

• Typically painless and multiple in number 5
• Disrupted or absent skin lines across the lesion distinguish warts from corns/calluses 3
• Pruritus is NOT characteristic of verruca vulgaris and suggests alternative diagnoses such as lichen planus 6
• Lesions can persist for years with minimal inflammation 1

Epidemiology and Natural History

• Affects 5-30% of children and young adults, though can occur at any age 1, 5
• In children, 50% clear spontaneously within 1 year and two-thirds by 2 years 1, 3
• In adults, warts persist much longer, with 5-10 years duration not being uncommon 1, 5
• Immunosuppressed patients develop large, extensive, treatment-resistant warts 1

Diagnosis

Diagnosis is primarily clinical, confirmed by paring down the lesion with a scalpel to reveal pathognomonic pinpoint bleeding from exposed capillary loops of elongated dermal papillae. 1, 3

Diagnostic Technique:

• Soak the lesion in warm water to soften tissue 3
• Carefully pare down superficial layers with a scalpel blade 3
• Inspect for pinpoint bleeding (diagnostic of warts) versus translucent core (corns) or homogenous keratin (calluses) 3
• Assess for disrupted skin lines characteristic of warts 3

Red Flag Features Requiring Biopsy Within 2 Weeks:

• Pruritus 5, 6
• Progressive growth 5
• Ulceration or spontaneous bleeding 5
• Change from soft to indurated/fixed consistency 5
• Pain or functional impairment 5
• Prolonged duration with atypical symptoms 6

Differential Diagnosis

Warts must be distinguished from other keratotic lesions through clinical examination or histology when atypical features are present. 1

On Hands and Feet:

• Corns: Occur at pressure points, paring reveals translucent central core without bleeding 3
• Calluses: Diffuse yellowish thickening at pressure areas, paring shows homogenous keratin without bleeding 3
• Actinic keratoses: Discrete erythematous scaly patches on sun-exposed skin in older adults 1, 3
• Squamous cell carcinoma: Must be excluded in atypical, long-standing, or rapidly growing lesions 1, 5
• Focal palmoplantar keratoderma 1
• Knuckle pads 1

On Limbs:

• Lichen planus: Hyperkeratotic lesions that may be pruritic 1
• Angiokeratoma 1
• Seborrhoeic keratoses 1

Special Considerations:

• Unusually severe or prolonged warts should prompt consideration of underlying immunodeficiency (lymphoma, idiopathic CD4 lymphocytopenia, HIV infection) 1
• In immunosuppressed patients, consider epidermodysplasia verruciformis-associated HPV types with malignant potential 1

Management

For immunocompetent patients with asymptomatic warts, expectant management is entirely acceptable given high spontaneous clearance rates, particularly in children. 1, 3

Treatment Indications:

• Warts causing discomfort or functional interference 1
• Cosmetic concerns, particularly on visible sites like the face 1
• Patient preference for active treatment 1

First-Line Treatment Options:

Salicylic acid 15-40% topical paints or ointments are recommended as first-line treatment (Level of evidence 1+, Strength A). 3

Cryotherapy with liquid nitrogen applied fortnightly for 3-4 months is also a recommended first-line option. 3

Treatment Selection Considerations:

• Anatomic site (avoid destructive treatments on face due to scarring risk) 3
• Size and number of warts 3
• Expense, efficacy, and convenience 3
• Potential adverse effects 3

Surgical Management:

• Complete surgical excision is the standard of care for atypical presentations or when biopsy is needed 5, 6
• Indicated for giant, chronic, isolated, recalcitrant warts unresponsive to conservative treatment 4
• Provides both diagnostic confirmation and definitive treatment 4

Critical Pitfalls and Caveats

• Wart treatments do not eradicate HPV infection; recurrence is common, typically at least 25% within 3 months with all modalities 3
• Never use destructive treatments on facial warts without extreme caution due to scarring risk 3
• Avoid overdebridement which can cause pain and tissue damage 3
• Do not use chemical corn removers or plasters on diabetic patients due to high complication risk 3
• Biopsy any lesion with red flag features within 2 weeks to avoid missing malignancy 5, 6
• Long-standing lesions may lose characteristic histopathologic features and HPV may not be detectable; examine multiple sections histopathologically 4
• Poor or absent response to treatment in immunosuppressed patients is expected 1

Patient Education

• HPV spreads through direct contact or environmental surfaces and may remain infectious for months or years 3
• Spontaneous clearance is common, especially in children (50% at 1 year, two-thirds by 2 years) 1, 3
• Adult warts persist longer (5-10 years not uncommon) and are slower to clear 1, 5
• Recurrence after treatment is common (at least 25% within 3 months) 3
• Avoid picking or manipulating warts to prevent autoinoculation and spread 2