Comorbidity-Guided Management of Pyoderma Gangrenosum: A Clinical Guide to Emerging Therapeutic Targets.

BACKGROUND: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis frequently associated with systemic comorbidities such as inflammatory bowel disease (IBD), arthritis, and hematologic disorders. Management remains challenging due to heterogeneous presentations and treatment responses. OBJECTIVE: To propose a comorbidity-guided therapeutic framework. METHODS: A clinical review of clinical trials, case series, and real-world reports on PG management was conducted. Emphasis was placed on immunopathologic pathways linking PG with major comorbidities and on therapeutic strategies employing biologic and small-molecule agents tailored to these associations. RESULTS: Comorbidity-directed therapy, such as TNF inhibition for IBD-associated PG, IL-1 blockade for autoinflammatory syndromes, and Janus kinase (JAK) inhibition for arthritis overlap, resulted in higher healing rates and lower relapse risk across studies. Real-world cases demonstrate that individualized therapy addressing the underlying systemic drivers of skin disease may yield more durable ulcer healing than empiric therapy alone. CONCLUSION: A comorbidity-guided approach personalizes PG therapy, aligning dermatologic and systemic management to improve healing, minimize recurrence, and optimize patient outcomes.