The dual potential of topical roflumilast: advancing psoriasis therapy and pioneering oral mucosal disease treatment.

BACKGROUND

Psoriasis and recurrent aphthous ulcers are chronic inflammatory disorders characterized by overlapping immunopathogenic mechanisms, including dysregulation of the interleukin-23/T helper 17 cell (IL-23/Th17) axis, innate immune hyperactivation, and microbial-immune dysbiosis. A shared molecular feature is aberrant phosphodiesterase-4 (PDE4) activity, a central regulator of cyclic adenosine monophosphate (cAMP) signaling and pro-inflammatory mediator production.

OBJECTIVE

This review aims to synthesize the shared immunopathological landscape between psoriasis and oral aphthous ulcers and to evaluate PDE4 inhibition as a unifying therapeutic strategy based on this common pathophysiology.

FINDINGS/

RESULTS

The analysis underscores significant mechanistic convergence between the two conditions, positioning PDE4 inhibition as a promising targeted approach. Roflumilast, a potent PDE4 inhibitor, exemplifies this translational potential. Its topical formulation (0.3% cream) is FDA-approved for plaque psoriasis, with phase 3 trials confirming sustained efficacy and a favorable safety profile. In parallel, systemic (oral) roflumilast demonstrates promising clinical activity in oral ulcer management, with studies in Behçet's disease and refractory aphthosis reporting substantial reductions (80-89%) in ulcer frequency and severity.

CONCLUSION

The shared pathophysiology between psoriasis and recurrent aphthous ulcers provides a strong rationale for repurposing PDE4 inhibitors across these conditions. This review advocates for accelerated translational efforts to evaluate topical roflumilast specifically for oral ulcer management and to broaden its therapeutic application across other chronic inflammatory diseases guided by precision immunomodulation principles.