Dual-Targeted Therapy in Refractory Pyoderma Gangrenosum: A Focused Systematic Review of Convergent Pathway Targeting

Refractory pyoderma gangrenosum (PG) may persist despite corticosteroids, ciclosporin, biologics or sequential treatment escalation. Dual-targeted therapy (DTT) is increasingly used in medically complex inflammatory bowel disease (IBD), but PG is often recorded only as an extraintestinal manifestation. We examined the direction, extractability and attribution limits of PG outcomes reported during concurrent DTT.

PubMed, Embase via Ovid and Web of Science Core Collection were searched from inception to 26 July 2026. Eligible reports described at least one patient with PG receiving concurrent systemic DTT, defined as biologic-biologic, biologic-Janus kinase (JAK) inhibitor or biologic-phosphodiesterase-4 inhibitor combinations. Screening and extraction were performed independently and in duplicate. The analytic unit was the PG exposure. Outcomes were retained as source-reported and were not pooled because PG assessment, follow-up and co-intervention reporting were non-standardised.

Fourteen reports described 17 PG exposures. Of these, 14 had an extractable PG-specific cutaneous outcome, all source-reported using non-standardised assessments as improved or resolved. This 14-of-14 pattern reflects the direction of published outcome-bearing observations, not a denominator-based response estimate. Three additional cohort-level records documented PG exposure without a separable cutaneous end-point. A total of 16 exposures were IBD-associated and 11 involved JAK-containing regimens. Individual regimen mapping, diagnostic ascertainment, follow-up and co-intervention reporting were frequently incomplete. All evidence was uncontrolled, safety reporting was limited and the complete exposure denominator was unknown.

Favourable PG outcomes were reported across several DTT pathway pairings, but these uncontrolled published observations do not establish efficacy, comparative advantage or added benefit from simultaneous pathway blockade. The next step is a dermatology-embedded prospective registry within IBD DTT programmes, with standardised PG diagnosis, lesion documentation, co-intervention recording and exposure-specific safety ascertainment. Until such evidence is available, DTT should remain an exceptional multidisciplinary consideration rather than an established PG treatment strategy.