Rosacea Research Digest - March 31, 2025
Recent research into new treatments, rosacea in early life, the microbiome, and more.
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.
Oxidative stress mediated by the NOX2/ROS/NF-κB signaling axis is involved in rosacea.
Wang Y, Long L, Chen M, Li J. Arch Dermatol Res. 2025 Feb 27;317(1):505. doi:10.1007/s00403-025-03898-5. PMID: 40014137.
Rosacea is a chronic inflammatory cutaneous disease characterized by a multifaceted pathogenesis. Extensive research has demonstrated that oxidative stress plays a pivotal role in the etiology of rosacea, mediating vascular alterations and inflammation cascades via the generation of reactive oxygen species (ROS). Nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) possesses the capacity to synthesize ROS and exhibits a strong correlation with diverse inflammatory processes. However, the effects of NOX2 in rosacea are unknown. Our findings revealed that NOX2 was highly expressed in rosacea. Inhibition of NOX2 improved markedly rosacea-like manifestations, encompassing reduced skin erythema and downregulated expression of pro-inflammatory cytokines and chemokines. Additionally, knockdown NOX2 in HaCaT keratinocytes significantly rescues TNF-α-induced oxidative stress and inflammation. Our study further elucidated that inhibition of NOX2 suppressed NF-κB activation in LL37-induced skin and LL37/ TNF-α-induced HaCaT keratinocytes. Our results demonstrate that NOX2 plays a proinflammatory role in rosacea by regulating the NF-κB signaling pathway.
A review on the mechanisms and clinical advances of JAK inhibitors in the treatment of rosacea.
Hu Y, Li B, Hu R, et al. J Cutan Med Surg. 2025 Mar 28:12034754251325482. doi:10.1177/12034754251325482. Epub ahead of print. PMID: 40152581.
Rosacea is a chronic inflammatory disease that primarily affects the facial area, with a complex pathogenesis and a variety of treatment options. In recent years, with deeper research into the pathogenesis of rosacea, it has been discovered that the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signalling pathway may be involved in the development of rosacea, and JAK inhibitors are expected to become a new therapeutic approach for rosacea. This paper reviews the mechanisms, clinical efficacy, and safety of JAK inhibitors in the treatment of rosacea.
Rosacea in childhood and adolescence: a review.
Korsing S, Stieler K, Pleyer U, et al. J Dtsch Dermatol Ges. 2025 Mar 22. Epub ahead of print. doi:10.1111/ddg.15693. PMID: 40119745.
Despite presenting with similar symptoms, triggers, and progression patterns as adults, rosacea in children and adolescents is frequently overlooked as a primary differential diagnosis. However, initial manifestations of classic clinical types can be observed from infancy onwards. The frequent association of childhood rosacea with ophthalmologic manifestations is of particular importance in addition to the knowledge of special subtypes such as idiopathic aseptic facial granuloma. Therapeutic options of pediatric rosacea partly overlap with those of common differential diagnoses such as acne vulgaris or perioral dermatitis. However, both the disease itself and its manifestation in this age group entail challenges in the selection of active ingredients and the development of therapeutic concepts. In addition, advice on triggering and aggravation factors is required in order to provide optimal long-term support for those affected.
Novel thermosensitive hydrogel encapsulated carvedilol for the treatment of rosacea.
Chen H, Zhang Z, Qi J, et al. ACS Omega. 2025 Feb 19;10(8):7964-7972. doi:10.1021/acsomega.4c08884. PMID: 40060832; PMCID: PMC11886671.
Background: Carvedilol can be used in the treatment of rosacea. However, their oral administration often results in a series of adverse effects. Purpose: A novel thermosensitive hydrogel was developed to improve the administration of carvedilol in the treatment of rosacea and to evaluate its safety and efficacy. Methods: The thermosensitive hydrogel was formulated using varying ratios of poloxamer 407 (P407) and poloxamer 188 (P188), with carvedilol being encapsulated during the process. The gel temperature and time of the hydrogel were observed, its phase transition was assessed through the inverted tube test, its microstructure was examined using scanning electron microscopy (SEM), and its characteristic functional groups were identified with Fourier transform infrared spectrometry (FTIR). The hydrogel's therapeutic efficacy on a rosacea-like phenotype in mice was evaluated through in vitro experiments. Results: It is observed that the microstructure of the hydrogel possesses a porous structure, with pores uniformly arranged in a square lattice measuring 8-12 μm in diameter. Thermosensitive hydrogel encapsulated carvedilol (Car-P40724/P1881) had favorable drug release rate and swelling properties. Live/dead cell assays indicated minimal toxicity of the hydrogel to HaCaT cells, and the carvedilol encapsulated with hydrogel possessed a better therapeutic effect on the rosacea-like phenotype in mice. Conclusion: Car-P40724/P1881 was not significantly cytotoxic and possessed good cellular biocompatibility. Furthermore, it exhibits a good therapeutic effect on rosacea-associated facial flushing and erythema. It possesses some anti-inflammatory properties and exhibits great potential for future use in rosacea treatment.
Evaluation of the safety and effectiveness of combination therapy with 1% ivermectin solution in moderate to severe rosacea: a cohort study.
Keneshbek Kyzy K, Omurzakova A, Azhikulova V, et al. J Med Microbiol. 2025 Mar;74(3). doi:10.1099/jmm.0.001974. PMID: 40052667.
Introduction. Rosacea is a common chronic dermatological disease that negatively affects the quality of life of patients. Hypothesis. Combination therapy with 1% ivermectin solution alongside systemic treatment methods is more effective in reducing the severity of moderate to severe papulopustular rosacea symptoms compared with traditional treatment methods alone. Aim. This study is aimed at finding new approaches to the treatment of moderate and severe forms of rosacea. Methodology. This research compared the main group receiving ivermectin with a control group getting conventional treatment to assess the safety and efficacy of 1% ivermectin combination therapy in 70 individuals with moderate to severe rosacea. At weeks 2, 4 and 8, the dynamics of clinical symptoms were evaluated using a 4-point scale. Results. The use of combination therapy with ivermectin led to a more pronounced improvement in the clinical picture. Already at week 4, a 48-54% decrease in symptoms was recorded in the main group, while in the control group, it was only by 25-30%. By week 8, an almost complete reduction of the main manifestations was observed in the main group (78-88% decrease). Regression analysis confirmed that combination therapy with ivermectin was a key factor determining a more substantial clinical improvement, regardless of age, gender and the initial severity of the patient's condition. In addition, a much more pronounced decrease in the number of Demodex ticks was recorded in the main group. The effectiveness of combination therapy with ivermectin did not depend on the demographic or clinical characteristics of patients, which makes it a universal method of treating rosacea. No serious side effects have been reported in any patient receiving combination therapy, which indicates its safety. Conclusion. This approach can be a valuable addition to existing strategies for the treatment of this chronic dermatological disease.
Comparative analysis of the skin microbiota of rosacea, steroid-induced rosacea and perioral dermatitis.
Mochizuki A, Osaka T, Fukuya Y, et al. Exp Dermatol. 2025 Mar;34(3):e70084. doi:10.1111/exd.70084. PMID: 40095381.
Rosacea, steroid-induced rosacea, also known as corticosteroid-induced rosacea-like dermatitis, and perioral dermatitis cause erythema, red papules, and pustules on the face. Tetracycline therapy is often effective for these skin diseases, suggesting that skin bacteria may be involved in these pathogeneses. To explore the etiologic significance of skin bacteria, we examined the microbiota of rosacea, steroid-induced rosacea, and perioral dermatitis, as well as healthy participants (n=50), using swab specimens that were obtained by rubbing the skin surface and vellus hair specimens that were collected from the perioral lesions. Skin microbiota was determined with short-amplicon sequence analysis for 16S rRNA gene (V1-V2 regions). Comparative analysis of the microbiota showed that the bacterial composition in perioral dermatitis cases was clearly different from that of rosacea cases and healthy participants but similar to that of some cases of steroid-induced rosacea. The uncultured Neisseriales bacterium was prevalent in the skin microbiota of some cases of steroid-induced rosacea and perioral dermatitis cases. After antibiotic therapy to steroid-induced rosacea and perioral dermatitis cases, the uncultured Neisseriales bacterium disappeared with improvement of the skin rash. These results indicate that the skin bacteria involving unculturable bacterium in the skin microbiota had a significant impact on steroid-induced rosacea and perioral dermatitis pathogeneses, and that microbiota-targeted treatment may be effective for steroid-induced rosacea and perioral dermatitis.
Case Reports
Rosacea-like eruptions associated with upadacitinib in atopic dermatitis: two case reports and management strategies.
Paganini C, Mortato E, Tofani L, et al. Dermatol Reports. 2025 Mar 4. Epub ahead of print. doi:10.4081/dr.2025.10193. PMID: 40047224.
Atopic dermatitis (AD) is a chronic inflammatory skin disease often requiring systemic therapies for moderate-to-severe cases. Janus kinase (JAK) inhibitors, including upadacitinib, have emerged as effective options, targeting pro-inflammatory cytokines involved in AD pathogenesis. However, adverse dermatologic reactions, such as rosacea-like eruptions, have been observed, potentially linked to immune pathway modulation. This report describes two patients with severe AD who achieved complete disease clearance with upadacitinib but developed rosacea-like eruptions. Both cases required discontinuation of the drug and treatment with antibiotics, which resolved the symptoms. However, withdrawal led to AD flares in one patient, necessitating the reintroduction of upadacitinib at a reduced dose combined with prophylactic antibiotics. These cases underscore the efficacy of JAK inhibitors while highlighting the challenge of managing adverse effects. Individualized treatment approaches, including dose adjustments and adjunctive therapies, are essential for balancing AD control with tolerability. Further research is needed to optimize the management of these reactions.
Recurrence of rosacea induced by compound vitamin tablets: a case report.
Feng HS, Zhang WT, Xi ZY, et al. J Inflamm Res. 2025 Mar 6;18:3311-3319. doi:10.2147/JIR.S507861. PMID: 40065906; PMCID: PMC11892490.
We present a case of rosacea recurrence in a 37-year-old woman associated with the intake of compound vitamin tablets during the preconception period, with a Naranjo score of 7. These tablets, commonly used for nutritional supplementation to prevent anemia, contain a variety of vitamins, minerals, and trace elements. Despite their widespread use, reports of such supplements causing rosacea recurrence are rare. In this case, the patient experienced a recurrence of facial redness, stinging, and burning after taking the tablets on two separate occasions. Skin dermatoscopy, VISIA imaging, Clinician's Erythema Assessment (CEA), Investigator's Global Assessment (IGA), and Visual Analogue Scale (VAS) all confirmed the recurrence of rosacea. Given her intention to conceive, symptomatic treatment with emollient and reparative dressings was administered. The patient's symptoms gradually resolved after discontinuing the medication, with no recurrence observed during follow-up visits. Women with a history of rosacea should avoid these tablets during preconception, pregnancy, and lactation to prevent recurrence and should choose supplements carefully to minimize the risk of rosacea flare-ups.
Ablative CO2 laser treatment of rhinophyma in people of color: a case series.
Nganzeu CG, Lopez A, Brennan TE. Plast Reconstr Surg Glob Open. 2025 Mar 7;13(3):e6616. doi:10.1097/GOX.0000000000006616. PMID: 40061169; PMCID: PMC11888977.
Rhinophyma is the result of progressive acne rosacea, which results in hypertrophy and fibrosis of sebaceous glands and connective tissues of the nose. The skin soft tissue envelope of the nose becomes bulkier and heavier relative to the underlying structural supportive framework of the nose over time, resulting in nasal airway obstruction and disfigurement that adversely impact quality of life. It is classically taught that rhinophyma is a disease that more commonly affects men, White people, and those in middle age. There are multiple treatment modalities available for rhinophyma aimed at surgical reduction of the overgrown skin soft tissue envelope, including CO2 laser-assisted surgical excision. Rhinophyma also occurs in people of color, including Latin Americans, Native Americans, Black people, and others, although the condition is rare in these populations. There is less written about the limits of laser-related treatments in these populations. We present a case series of 7 patients with melanated skin and moderate to severe rhinophyma who were treated with CO2 laser excision, with significant improvement in nasal appearance and functional nasal obstruction as a result. Three patients in the series developed some degree of scarring in the supratip and tip region that did not significantly deter the overall improvement in nasal aesthetics from treating the disease. A more conservative treatment plan with respect to the depth of resection may have limited scarring, or perhaps the traditional teaching to approach laser treatments in patients with melanated skin with caution due to risks of scarring is supported here.
News
National Rosacea Society Introduces Updated Rosacea Treatment Algorithms
Rosacea.org
The National Rosacea Society today announced it has published an updated version of its Rosacea Treatment Algorithms in the Physicians section of its website, rosacea.org. The new version is organized according to the phenotype model established by the 2017 updated standard classification and pathophysiology of rosacea, and suggests therapeutic approaches to mild, moderate and severe presentations of each phenotype based on the 2019 update to the standard management options for rosacea, as well as the original management options and studies of more recently developed therapies.
New Study Compares Topical Serum and Pulse Light Therapy for Rosacea
Dermatology Times
A comparative study between topical PHA and intense pulse light (IPL) therapy was conducted to determine what works better to improve mild erythema and flushing associated with rosacea. Erythema is found in nearly 50% of rosacea cases. Although both therapies were effective, IPL had a greater improvement on the overall appearance of the face, but it is up to each patient to determine which better suits their lifestyle.
Emrosi Officially Launched for Treatment of Inflammatory Rosacea
Practical Dermatology
Journey Medical has announced the launch and initial prescriptions for Emrosi for the treatment of inflammatory lesions of rosacea in adults.
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