The Rosacea Research Digest from the National Rosacea Society keeps you up to date on recently published basic and clinical research on rosacea, as well as news, reviews, and presentations. It goes out on the last weekday of each month.

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Research

Efficacy, safety, and tolerability of oral DFD-29, a low-dose formulation of minocycline, in rosacea: two phase 3 randomized clinical trials.

Bhatia N, Del Rosso J, Stein Gold L, et al. JAMA Dermatol. 2025 Mar 5:e246542. Epub ahead of print. doi:10.1001/jamadermatol.2024.6542. PMID: 40042869; PMCID: PMC11883608.

Introduction: A low-dose modified formulation of minocycline hydrochloride, DFD-29, is under evaluation for treating papulopustular rosacea (PPR). Objective: To determine the efficacy and safety of DFD-29, 40 mg, compared with doxycycline, 40 mg, and placebo for treating PPR. Design, setting, and participants: This study included data from 2 double-blind, placebo-controlled, phase 3 randomized clinical trials (MVOR-1 and MVOR-2) conducted between March 2022 and May 2023 at 61 centers in the US and Germany. Healthy adults 18 years and older with moderate to severe PPR were included. Interventions: Participants were randomized 3:3:2 to oral DFD-29 (minocycline hydrochloride capsules), 40 mg; doxycycline, 40 mg; or placebo once daily for 16 weeks. Main outcomes and measures: The coprimary efficacy outcomes were (1) proportion of participants with Investigator's Global Assessment (IGA) treatment success with DFD-29 vs placebo and (2) total inflammatory lesion count reductions with DFD-29 vs placebo. Secondary outcomes included comparisons between DFD-29 and doxycycline in coprimary outcomes and between DFD-29 and placebo in erythema reduction. Results: Of 653 participants enrolled, 323 were randomized in MVOR-1 (247 [76.5%] women; mean [SD] age, 47.2 [13.7] years) and 330 were randomized in MVOR-2 (249 [75.5%] women; mean [SD] age, 51.6 [14.0] years). DFD-29 demonstrated superior efficacy in IGA success rates compared with placebo (MVOR-1: treatment difference [TD], 32.9%; 95% CI, 19.6-46.2; P < .001; MVOR-2: TD, 34.1%; 95% CI, 21.3-46.8; P < .001) and compared with doxycycline (MVOR-1: TD, 18.0%; 95% CI, 5.0-31.1; P = .01; MVOR-2: TD, 28.3%; 95% CI, 17.4-39.3; P < .001). DFD-29 also showed superior efficacy in least-squares mean reductions in total inflammatory lesions vs placebo (MVOR-1: TD, -9.2; 95% CI, -11.5 to -6.9; P < .001; MVOR-2: TD, -6.8; 95% CI, -8.9 to -4.8; P < .001) and doxycycline (MVOR-1: TD, -4.7; 95% CI, -6.7 to -2.8; P < .001; MVOR-2: TD, -3.5; 95% CI, -5.4 to -1.6; P < .001). Adverse events with DFD-29, doxycycline, and placebo were reported in 32 of 121 (26.4%), 25 of 116 (21.6%), and 27 of 76 (35.5%), respectively, in MVOR-1 and 51 of 122 (41.8%), 40 of 121 (33.1%), and 30 of 82 (36.6%), respectively, in MVOR-2. The most common adverse events with DFD-29, doxycycline, and placebo were nasopharyngitis, reported in 4 of 121 (3.3%), 2 of 116 (1.7%), and 3 of 76 (3.9%), respectively, in MVOR-1 and 13 of 122 (10.7%), 10 of 121 (8.3%), and 13 of 82 (15.9%), respectively, in MVOR-2, and COVID-19, reported in 4 of 121 (3.3%), 3 of 116 (2.6%), and 4 of 76 (5.3%) in MVOR-1 and 7 of 122 (5.7%), 8 of 121 (6.6%), and 5 of 82 (6.1%) in MVOR-2. Conclusions and relevance: In this study, DFD-29 was superior in efficacy to both doxycycline and placebo and demonstrated a favorable risk-benefit profile in the treatment of PPR.

Managing a burning face: clinical manifestations and therapeutic approaches for neurogenic rosacea.

Aedo G, Chahuán M, Gatica E, et al. Int J Mol Sci. 2025 Mar 6;26(5):2366. doi:10.3390/ijms26052366. PMID: 40076987; PMCID: PMC11901027.

Rosacea is a common chronic inflammatory condition primarily affecting middle-aged women. It presents with flushing, erythema, telangiectasia, papules, pustules, phymatous changes, and ocular involvement. Although typically grouped into four subtypes – erythematotelangiectatic, papulopustular, ocular, and phymatous – overlapping features often favor a phenotypic diagnostic approach. Neurogenic rosacea (NR) has emerged as a distinct subgroup featuring distinguishing features such as peripheral facial erythema, severe burning and stinging sensations, and resistance to standard rosacea therapies. Recent insights into the pathophysiology of NR propose neural dysregulation as the main driver of the condition. Specifically, the activation of TRP channels at cutaneous sensory nerve endings in the dermis triggers the release of vasoactive peptides, driving neuroinflammation and resulting in burning and stinging. Additionally, there is a marked association with neuropsychiatric comorbidities, which would further mediate the pathogenesis of the condition. In line with this pathophysiological model, NR often fails to respond to conventional rosacea treatments. Instead, patients benefit more from antidepressants and neuroleptic agents that help modulate neuronal activity and alleviate symptoms. This review explores and summarizes the scientific evidence regarding the new insights on disease pathogenesis, clinical manifestations, and proposed treatments for NR.

Probiotics and diet in rosacea: current evidence and future perspectives.

Manfredini M, Barbieri M, Milandri M, Longo C. Biomolecules. 2025 Mar 13;15(3):411. doi:10.3390/biom15030411. PMID: 40149947.

Rosacea is a common inflammatory skin disease, characterized by erythema, papules and pustules. The pathophysiology of rosacea remains unclear, but the complex interplay between environmental and genetic factors may act as a trigger to an abnormal innate immune response associated with a multifaceted neurovascular reaction. Increasing evidence suggests that the gut microbiota is significantly involved in the pathogenesis of rosacea, playing an important role in the inflammatory cutaneous response. Dysbiosis, small intestinal bacterial overgrowth, Helicobacter pylori infection and innate immune system dysregulation mutually contribute to the pathophysiology of rosacea, but more extensive future research is needed to better clarify their precise mechanisms of action. Many dietary triggers have been postulated for this disease; however, there is a lack of well-made and controlled studies able to undoubtedly demonstrate a causal relationship between rosacea and diet. We analyzed the available studies on the role of diet and gut microbiome in rosacea and the positive clinical effects reported by the current literature on probiotics, prebiotics, postbiotics and nutrients. Ultimately, this article improves our understanding of the gut-skin axis in rosacea, focusing on how probiotic supplementation and diet could improve the clinical management of patients affected by this common and debilitating disease.