Discussion

PG remains a diagnostic challenge because histopathologic findings may vary according to lesion stage, biopsy site, chronicity, and previous treatment exposure.3,4 Although a neutrophilic infiltrate represents the major Delphi criterion, late ulcerative lesions may demonstrate mixed or predominantly lymphocytic inflammation, reinforcing that PG is fundamentally a clinicopathologic diagnosis.4

Drug-associated PG has gained increasing recognition in recent years, particularly in the context of biologic therapies capable of disrupting cytokine balance and neutrophil homeostasis.5 Biologic agents, especially tumor necrosis factor and IL-17 inhibitors, have been associated with paradoxical inflammatory reactions.6,7 Although secukinumab has demonstrated substantial efficacy in psoriasis treatment, paradoxical neutrophilic dermatoses including PG have rarely been reported.6, 7, 8, 9, 10 Recognition of this phenomenon is essential, as it may be misinterpreted as disease progression, infection, or treatment failure.

Our patient fulfilled several Delphi minor criteria, including exclusion of infection, rapidly progressive painful ulceration, violaceous undermined borders, underlying inflammatory disease, and significant improvement following immunosuppressive therapy. Importantly, the initial gluteal and posterior thigh lesions were interpreted as recurrent furunculosis before progression to more characteristic ulcerative lesions, illustrating a frequent diagnostic pitfall in PG.

The pathophysiology of paradoxical PG associated with IL-17 inhibition remains incompletely understood. One proposed mechanism involves cytokine imbalance following IL-17 blockade, leading to compensatory activation of inflammatory pathways and neutrophil dysregulation.3,10 Interestingly, IL-17 inhibitors have also been reported as therapeutic options for refractory PG,6 highlighting the paradoxical and bidirectional role of cytokine modulation.

Most previously reported cases of secukinumab-associated PG involved the lower extremities and demonstrated classic neutrophilic infiltrates.7, 8, 9, 10 In contrast, our case was notable for exuberant scalp involvement, multifocal progression, and less characteristic histopathologic findings. Such an unusual clinical presentation may suggest that paradoxical drug-induced PG can manifest differently from classic PG, potentially contributing to diagnostic delay. These findings emphasize the importance of integrating clinical, histopathologic, and microbiological data for diagnosis.

The close temporal relationship between secukinumab initiation and lesion onset, followed by rapid pain improvement after corticosteroid therapy and progressive healing after drug discontinuation and cyclosporine initiation, strongly supported a probable paradoxical association.