A leprosy patient develops erythema nodosum leprosum (ENL, Type 2 lepra reaction). The drug of choice for managing severe ENL is thalidomide. Its mechanism in ENL involves:
- A Inhibition of dihydrofolate reductase, suppressing rapidly proliferating immune effector cells
- B Blocking leukotriene B4 receptors on neutrophils to prevent immune complex-mediated inflammation
- C Inhibition of IL-6 receptor signalling, suppressing acute-phase protein synthesis
- D Selective inhibition of TNF-alpha production from macrophages by destabilising TNF-alpha mRNA and blocking NF-kB signalling ✓
Explanation
Thalidomide is the drug of choice for severe or recurrent ENL. Its immunomodulatory mechanism involves inhibition of TNF-alpha production by macrophages through destabilisation of TNF-alpha mRNA (reducing its half-life) and inhibition of NF-kB activation. Since ENL is characterised by immune complex deposition, neutrophil infiltration, and massive TNF-alpha-driven inflammation, TNF inhibition is highly effective. Thalidomide also modulates T-cell co-stimulation via cereblon (CRBN) E3 ligase. Its severe teratogenicity (phocomelia) mandates strict contraception in women of childbearing age.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.