A 32-year-old man with Crohn's disease on infliximab develops fever, night sweats, and pulmonary infiltrates. BAL culture reveals Histoplasma capsulatum. Suppression of which inflammatory pathway by infliximab predisposes to this fungal infection?
- A IL-6 signaling (tocilizumab targets this pathway)
- B IL-12/IL-23 axis (ustekinumab targets p40 subunit)
- C JAK-STAT pathway (tofacitinib targets JAK1/JAK3)
- D TNF-alpha-dependent granuloma maintenance — TNF blockade disrupts granuloma integrity allowing mycobacterial/fungal reactivation ✓
Explanation
TNF-alpha is essential for formation and maintenance of granulomas that contain intracellular pathogens such as Mycobacterium tuberculosis, Histoplasma, and Listeria. Infliximab (anti-TNF-alpha monoclonal antibody) disrupts the continuous TNF signaling required to maintain granuloma structural integrity; macrophage activation, epithelioid cell formation, and giant cell function all depend on TNF. This explains the dramatically increased risk of TB reactivation (and primary histoplasmosis, coccidioidomycosis) with anti-TNF biologics. Screening with IGRA/TST before infliximab is a guideline recommendation.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.