Combination Therapy with Oral Doxycycline and Intradermal Botulinum Toxin Type A for Moderate-to-Severe Rosacea: A Randomized Controlled Trial

Abstract Background: Rosacea is a chronic inflammatory skin disorder, particularly challenging in moderate-to-severe cases, characterized by symptoms such as facial papules, pustules, erythema, flushing, and telangiectasia, which severely impact quality of life. Although oral doxycycline is a primary treatment, its efficacy against erythema is limited, necessitating the exploration of combination therapies. Intradermal botulinum toxin type A (BTX) has shown promise in managing facial erythema and flushing, but its combined use with doxycycline has not been evaluated. Objectives: This study aims to evaluate the effectiveness and safety of combining oral doxycycline with intradermal BTX (combination therapy) versus doxycycline with normal saline (monotherapy) in treating moderate-to-severe rosacea. Methods: A randomized, controlled trial was conducted with 46 participants aged 18 and older, diagnosed with moderate-to-severe rosacea. Participants were randomized to receive either combination therapy (doxycycline and BTX) or monotherapy (doxycycline and normal saline) for three months. Efficacy was assessed using the Clinician Erythema Assessment (CEA), Global Flushing Severity Score (GFSS), Investigator Global Assessment (IGA), telangiectasia degree, and Dermatology Life Quality Index (DLQI). Safety evaluations included monitoring adverse reactions. Results: Both groups showed significant reductions in CEA scores from baseline, with combination therapy demonstrating greater improvement ( P < 0.001). Combination therapy also significantly reduced GFSS and IGA scores compared to monotherapy ( P < 0.05). No significant changes were observed in the degree of telangiectasia. DLQI scores improved significantly in both groups, with greater reductions in the combination therapy group ( P < 0.05). Common adverse events, including injection site pain, erythema, and oedema, were tolerable and comparable between groups. Conclusion: The combination of oral doxycycline and intradermal BTX is more effective than doxycycline monotherapy in reducing erythema, flushing, and inflammatory lesions in moderate-to-severe rosacea, with a comparable safety profile. This combination therapy offers a promising approach for comprehensive management of rosacea symptoms.