What is the most direct diagnostic approach for a patient suspected of having tuberculosis (TB) of the skin?

Diagnostic Testing for Cutaneous Tuberculosis

The most direct diagnostic approach for cutaneous TB is tissue biopsy with mycobacterial culture on both liquid and solid media, which remains the gold standard despite low sensitivity (16.3%), because it enables definitive species identification and drug susceptibility testing—critical given rising multidrug resistance. 1

Primary Diagnostic Strategy

Tissue Biopsy and Culture

• Obtain a skin biopsy from the active border of the lesion and send for mycobacterial culture on both liquid and solid media as the definitive diagnostic test 1
• While sensitivity is only 16.3% for cutaneous lesions, culture is essential because it provides species identification and drug susceptibility testing, which directly impacts treatment decisions and patient outcomes 1
• The low yield means negative cultures do not exclude the diagnosis, requiring integration with other diagnostic modalities 1

Molecular Testing

• Perform DNA PCR (such as Xpert MTB/RIF) when histopathology is inconclusive, as it provides rapid results within 1-2 days with 24.5% sensitivity in cutaneous lesions 1
• In immunocompromised patients, use rapid molecular testing with Xpert MTB/RIF for simultaneous TB confirmation and rifampin resistance detection, given their higher risk of disseminated disease and atypical presentations 1

Histopathology

• Send biopsy tissue for histopathologic examination looking for granulomatous inflammation with or without caseation necrosis 2
• Acid-fast bacilli (AFB) staining should be performed on tissue sections, though sensitivity is limited 1

Adjunctive Testing

Tuberculin Skin Testing

• PPD skin testing has limited diagnostic value for active cutaneous TB but helps establish TB infection status 1
• Use Mantoux technique: inject 0.1 mL of PPD (5 TU) intracutaneously on forearm, creating a 6-10 mm wheal 3, 1
• Read results between 48-72 hours by trained personnel; measure only induration (not erythema) in millimeters 3
• Interpretation depends on patient risk factors: >5 mm is positive in immunocompromised, HIV-infected, or recent TB contacts 1
• Critical caveat: PPD testing cannot distinguish active disease from latent infection and has reduced specificity due to BCG vaccination 4, 5

Interferon-Gamma Release Assays (IGRAs)

• IGRAs (QuantiFERON, T-SPOT.TB) are alternatives to TST with similar performance characteristics 6
• These tests help establish TB infection status but do not differentiate active from latent disease 5, 7

Mandatory Evaluation for Systemic Involvement

Pulmonary Assessment

• All patients with cutaneous TB require chest radiography to assess for pulmonary TB, which is present in 93.78% of patients with any form of TB 1
• If pulmonary symptoms are present, collect three sputum specimens on different days for AFB smear, culture, and nucleic acid amplification testing 1
• Upper lobe or superior-segment lower lobe fibro-cavitary disease on chest radiograph warrants respiratory isolation and sputum culture 3

Additional Considerations

• For immunocompromised patients (particularly those with low CD4 counts), consider CT imaging even with normal chest radiographs, as they may have subtle parenchymal disease or abnormal lymph nodes 3
• Perform full medical evaluation in immunosuppressed patients regardless of skin test results, as anergy is common 1

Reporting Requirements

• Both suspected and confirmed cases of cutaneous TB must be reported to local or state health departments 5

Common Pitfalls to Avoid

• Do not rely solely on PPD or IGRA results to diagnose active cutaneous TB—these only indicate infection status 1, 5
• Do not accept patient self-reading of PPD tests; only trained personnel should interpret results 3
• Do not assume isolated cutaneous disease without comprehensive evaluation for pulmonary and systemic involvement 1
• In immunocompromised patients, maintain a lower threshold for aggressive diagnostic workup given atypical presentations 1