How do I differentiate a plantar wart from tuberculosis verrucosa cutis and what are the appropriate treatments for each?

Differentiating Plantar Wart from Tuberculosis Verrucosa Cutis

Tuberculosis verrucosa cutis (TVC) on the foot should be suspected when a verrucous lesion persists for years despite standard wart treatments, particularly in patients from endemic areas or with positive tuberculin testing, whereas typical plantar warts respond to treatment within months and show characteristic pinpoint bleeding on paring. 1, 2

Key Clinical Differentiating Features

Plantar Wart Characteristics

• Duration: Spontaneous clearance typically occurs within 1-2 years in children (50% at 1 year, 67% by 2 years), though adult warts may persist 5-10 years 3
• Paring test: Reveals pinpoint bleeding as capillary loops of elongated dermal papillae are exposed 3
• Location: Weight-bearing areas of the sole, often multiple lesions 3
• Response to treatment: Shows improvement with salicylic acid or cryotherapy within 3-4 months 4

Tuberculosis Verrucosa Cutis Characteristics

• Duration: Extremely indolent, persisting for decades (cases reported lasting 20-40 years) 1, 5
• Clinical appearance: Well-defined warty plaques that may present as diffuse plantar keratoderma or verrucous plaques with yellow-red crusts and central healing 2, 6
• Geographic/demographic clues: More common in patients from TB-endemic areas (e.g., Indian subcontinent) 1
• Treatment resistance: No response to standard wart therapies over months to years 1, 2

Diagnostic Algorithm

Step 1: Clinical Assessment

• Measure duration: If present >2 years without spontaneous improvement, consider TVC 1, 5
• Assess treatment response: Failure of 3-4 months of salicylic acid therapy or multiple cryotherapy sessions suggests alternative diagnosis 4
• Evaluate morphology: Diffuse keratoderma pattern or plaques with central healing favor TVC over typical plantar wart 2, 6

Step 2: Initial Testing

• Tuberculin skin testing (Heaf or Mantoux): Grade IV positive Heaf test supports TVC diagnosis 1
• Interferon-gamma release assay (IGRA): Positive result supports TVC even when other tests are negative 5
• Chest radiograph: Rule out pulmonary tuberculosis 1, 5

Step 3: Tissue Diagnosis (Critical for TVC)

• Multiple deep biopsies required: Single biopsy often insufficient; TVC is paucibacillary with few organisms 1, 6
• Histopathology: Look for granulomatous inflammation with pseudoepitheliomatous hyperplasia 2, 6
• Culture: Mycobacterium tuberculosis culture may require multiple attempts and takes weeks 1, 6
• Molecular testing: PCR/GeneXpert may be negative due to paucibacillary nature but cannot rule out TVC 6, 5

Critical pitfall: Ziehl-Neelsen staining and culture are frequently negative in TVC due to the paucibacillary nature of the lesion, so negative results do not exclude the diagnosis 6, 5

Step 4: Therapeutic Trial (When Diagnosis Uncertain)

• Indication: Strong clinical suspicion with negative microbiological tests but positive IGRA or tuberculin test 5
• Regimen: Category 1 antituberculosis treatment (isoniazid, rifampin, pyrazinamide, ethambutol) 5, 7
• Response timeline: Improvement visible within 3 weeks; continue for 6 months total 5, 7
• Diagnostic confirmation: Significant regression with antituberculosis therapy confirms TVC diagnosis 5

Treatment Protocols

For Confirmed Plantar Wart

First-line: Salicylic acid 15-26% applied daily after paring with occlusion for 3-4 months (Strength of Recommendation A) 4

Second-line options (if no response after 3 months):

• Cryotherapy every 2-4 weeks for at least 3 months 4
• 5-Fluorouracil 5% cream under occlusion achieving 95% clearance after 12 weeks 4
• Contact immunotherapy with DPC or SADBE (88% clearance rate) 4
• Intralesional Candida antigen (47-87% clearance) 4

Third-line: Bleomycin intralesional injection 0.1-1 U/mL for resistant single lesions 4

For Confirmed Tuberculosis Verrucosa Cutis

Standard treatment: Category 1 antituberculosis therapy for 6 months 5

• Intensive phase (2 months): Isoniazid, rifampin, pyrazinamide, ethambutol
• Continuation phase (4 months): Isoniazid and rifampin

Monitoring: Expect visible improvement within 3 weeks, with significant regression by 6 months 5, 7

Critical Clinical Pearls

• Never dismiss a "wart" that has been present for >2 years without improvement - this duration strongly suggests an alternative diagnosis like TVC 1, 2
• Correlation of clinical manifestations, dermoscopy, and histopathology can establish TVC diagnosis when culture is negative, which occurs frequently due to the paucibacillary nature 6
• Multiple biopsies may be necessary - the first or second biopsy may miss the diagnosis 1
• Geographic origin matters - maintain higher suspicion for TVC in patients from TB-endemic regions 1
• Therapeutic trial is justified when clinical suspicion is high despite negative microbiological tests, particularly with positive IGRA or tuberculin testing 5