Which test is most important to order before initiating methotrexate therapy?

• A. CBC
• B. LFTs
• C. PPD
• D. HIV

Answer: (C)

Screening for latent infection is a priority before starting immunosuppressive therapy like methotrexate because this medication can unmask or worsen infections. The most important test to order is a tuberculin skin test (PPD) to detect latent tuberculosis. If the test is positive, latent TB should be treated before initiating methotrexate to prevent reactivation, which can be severe when immune suppression is started. If the test is negative, you can proceed with methotrexate, but you’ll still monitor regularly for toxicity.

Baseline labs such as CBC and liver function tests are important to monitor potential cytopenias and hepatotoxicity from methotrexate, but they don’t address the infection risk that could be unmasked by immunosuppression. HIV testing is prudent in patients with risk factors, but it is not the primary pre-treatment test used to mitigate methotrexate-related complications.