Mantoux Test in Immunocompromised Patients with Suspected Cutaneous Tuberculosis
Limited Diagnostic Value with Significant Caveats
The Mantoux test has poor diagnostic accuracy for cutaneous tuberculosis in immunocompromised patients and should not be relied upon as a primary diagnostic tool, though it remains part of the screening algorithm when combined with chest radiography and histopathology. 1
Key Limitations in Immunocompromised Hosts
Anergy Renders the Test Unreliable
HIV-infected persons and other immunocompromised patients have compromised ability to react to tuberculin skin testing due to cutaneous anergy, making negative results uninterpretable. 2
Impaired delayed-type hypersensitivity (DTH) response is directly related to decreasing CD4+ T-lymphocyte counts, with anergy incidence increasing as immune function declines. 2
Anergy testing is no longer recommended routinely for screening M. tuberculosis infection in HIV-infected persons because of problems with standardization, reproducibility, and lack of benefit. 2
A negative PPD does not exclude tuberculosis infection in immunosuppressed patients—selective non-reactivity to PPD is a recognized phenomenon even when other antigens produce responses. 2
Poor Performance for Cutaneous Tuberculosis Specifically
In a study of 90 patients with doubtful cutaneous tuberculosis diagnoses, the Mantoux test showed an area under the ROC curve of only 0.66, with sensitivity of 58.97% and specificity of 62.50% at a 10mm cutoff. 1
The Mantoux test is of low accuracy in diagnosing doubtful cases of cutaneous tuberculosis, even in immunocompetent populations. 1
Interpretation Thresholds for Immunocompromised Patients
Use Lower Cutoffs to Maximize Sensitivity
For HIV-positive persons, organ transplant recipients, and patients on immunosuppressive therapy (equivalent to >15 mg/day prednisone for >1 month), induration ≥5 mm is considered positive. 2, 3
This lower threshold compensates for diminished immune response capacity but does not overcome the fundamental problem of anergy. 2
Tuberculin testing is not valid in patients already established on immunosuppressive therapy (e.g., methotrexate), as the test requires intact cell-mediated immunity. 2
Alternative Testing Strategies
IGRA Tests Are Preferred When Available
For immunocompromised patients, FDA-approved interferon-gamma release assays (IGRAs) are preferred over tuberculin skin testing because they are unaffected by immunosuppression to a lesser degree and have higher specificity. 4, 5
The T-SPOT.TB test may be more sensitive in patients on immunosuppressive drugs compared to standard tuberculin testing. 2
IGRAs measure T-cell production of interferon-gamma in response to M. tuberculosis-specific antigens and correlate more closely with exposure risk factors than the Mantoux test. 5
Practical Clinical Algorithm
When Cutaneous Tuberculosis Is Suspected in Immunocompromised Patients:
Perform chest radiography regardless of skin test results—this is mandatory to exclude pulmonary tuberculosis. 2, 6
Obtain skin biopsy for histopathology and mycobacterial culture, which remains the gold standard for diagnosis. 1
Consider Mantoux testing with ≥5mm threshold as supplementary information only, recognizing that negative results do not exclude disease. 2, 3
If IGRA testing is available, use it preferentially over Mantoux testing. 2, 4
Refer patients with positive screening tests or high clinical suspicion to a tuberculosis specialist for risk stratification and consideration of prophylactic therapy. 2
Critical Pitfalls to Avoid
Never rule out tuberculosis based on a negative Mantoux test in an immunocompromised patient—anergy makes the test uninterpretable. 2
Do not delay empiric antitubercular therapy in high-risk immunocompromised patients with compatible clinical and histopathologic findings while awaiting culture results. 2
Maintain high index of suspicion for tuberculosis throughout treatment with immunosuppressive agents and for 6 months after discontinuation. 2
BCG vaccination history does not contraindicate testing, and positive reactions should be interpreted as indicating true M. tuberculosis infection, especially in high-risk contexts. 4, 7