), a transient low-dose glucocorticoid pulse, and an optimized anti-inflammatory, antioxidant-rich physiological milieu delivered within a stress-free environment. In a cohort of four patients with PG refractory to conventional immunosuppressants, this 30-day protocol elicited a rapid and profound clinical response. Objective metrics demonstrated a mean ulcer area reduction exceeding 61% by Day 30, progressing to complete and sustained re-epithelialization in all subjects. This robust cutaneous healing occurred concurrently with the normalization of systemic inflammation (C-reactive protein) and a significant restoration of functional capacity, evidenced by a mean improvement of 35 points on the Anterior Knee Pain Scale. Critically, clinical remission was maintained throughout a 6-month surveillance period, establishing a definitive steroid-sparing effect. We propose this multisystem improvements emerge from rational polypharmacology, wherein the nanoengineered HgS core serves as a pivotal immunomodulatory node, potentially engaging master regulatory pathways like NF-κB to disrupt dysregulated cytokine circuitry. It transcends conventional combination therapy, introducing a paradigm for managing refractory autoinflammation through integrative systems and compelling a rigorous reappraisal of pharmaceutically refined traditional nanomedicines. This preliminary evidence establishes a compelling rationale for future research to deconstruct the system's architecture and validate its therapeutic potential.
P. et al. (Thu,) studied this question.