Usual interstitial pneumonia (UIP) on histology shows honeycombing, fibroblastic foci, and patchy fibrosis of varying age ('temporal heterogeneity'). Which feature best explains the poor response to immunosuppressive therapy in UIP/IPF?
- A UIP/IPF is driven by repeated epithelial microinjury and aberrant fibroblast activation, not primarily by inflammation — hence anti-inflammatory therapy is ineffective ✓
- B UIP has active lymphocytic alveolitis that is resistant to steroids
- C UIP fibrosis is mediated by eosinophilic inflammation that does not respond to corticosteroids
- D UIP has irreversible basement membrane calcification preventing drug penetration
Correct answer: A. UIP/IPF is driven by repeated epithelial microinjury and aberrant fibroblast activation, not primarily by inflammation — hence anti-inflammatory therapy is ineffective
Explanation
IPF/UIP is now understood as an epithelial-mesenchymal disorder driven by repeated microinjuries to alveolar epithelial cells, triggering aberrant TGF-beta-mediated fibroblast activation and myofibroblast differentiation rather than primary immune inflammation. This explains why immunosuppressants (including corticosteroids and cyclophosphamide) are ineffective or even harmful. Antifibrotic agents (pirfenidone, nintedanib) that target fibroblast signaling pathways slow disease progression.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.