Rosacea Research Digest - October 31, 2025
Alternative treatments, laser therapy, the exposome's role, 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
The role of skin barrier and immune abnormalities in the pathogenesis of Rosacea.
Chen LX, Hao PS. Clin Exp Med. 2025 Oct 25;25(1):324. DOI: 10.1007/s10238-025-01859-w. PMID: 41137965; PMCID: PMC12553588.
Rosacea is marked by a compromised skin barrier, abnormal immune responses, and vascular dysregulation. It typically manifests as persistent or intermittent flushing, along with papules and pustules. These symptoms are often accompanied by burning, itching, or stinging sensations that can significantly affect the physical and mental well-being of those affected. Multiple factors contribute to the increased sensitivity in rosacea-affected skin, including barrier dysfunction and inflammatory activation. While the pathogenesis of rosacea is not fully understood, compromised skin barriers and aberrant immune responses are recognized as key contributors. This review aims to summarize recent findings on rosacea and its underlying pathological mechanisms while exploring the interplay between abnormalities in the skin barrier and immune response. Consequently, we propose that targeting both the skin barrier and immune response may represent a novel therapeutic strategy for modulating the inflammatory pathways associated with rosacea.
Plant extracts in rosacea management: a narrative review.
Leti M, Garidou L, Cuisiat SV, et al. Dermatology. 2025 Oct 3:1-48. DOI: 10.1159/000548793. Epub ahead of print. PMID: 41042734.
Rosacea is a prevalent, chronic inflammatory skin disorder increasingly affecting middle-aged individuals worldwide. Characterized by facial erythema, flushing, papules, pustules, and telangiectasia, rosacea arises from complex, dysregulated immune responses with chronic inflammation and vascular instability. Given its multifactorial nature, treatment approaches focus on managing symptoms and often require a multidisciplinary strategy that integrates targeted skincare, topical and systemic therapies, and physical modalities to address the condition's diverse clinical manifestations, subtypes, and severity effectively. Validated conventional treatments, like metronidazole and azelaic acid, offer symptom relief to varying extents; however, many patients find these therapies insufficient, leading to a growing interest in alternative therapies. Dermocosmetic products containing natural ingredients, particularly botanicals, are gaining in popularity, driven not only by their reported anti-inflammatory properties and perceived favorable tolerability, but also because they often appear to align with the personal values and beliefs of many individuals, and offer a more holistic approach to care. Emerging clinical evidence suggests that plant-based ingredients may help alleviate rosacea symptoms by modulating inflammation, regulating keratinization, and supporting vascular health, thereby promoting skin restoration, vessel stability, and reduced sensitivity. This review provides an up-to-date summary of advancements in the use of botanical ingredients for the management of rosacea. By exploring both well-studied botanicals and emerging plant extracts, this review highlights the growing role of natural adjunctive treatments in rosacea care.
The exposomal imprint on rosacea: more than skin deep.
Grafanaki K, Bakoli Sgourou D, Maniatis A, Pasmatzi E. J Eur Acad Dermatol Venereol. 2025 Oct 13. Epub ahead of print. DOI: 10.1111/jdv.70112. PMID: 41081484.
Rosacea is a chronic, inflammatory dermatosis driven by a complex interplay of genetic, environmental and lifestyle factors, collectively known as the exposome. This review explores how intrinsic contributors such as genetic susceptibility, immune dysregulation, microbiome alterations, hormonal influences and psychosocial stress intersect with extrinsic triggers like ultraviolet radiation (UVR), air pollution, dietary factors, and climate variability to shape rosacea pathogenesis. Recent advances in single-cell transcriptomics have identified fibroblasts as key components of inflammatory and vascular pathways in rosacea. Concurrently, discoveries in non-coding RNAs and RNA modifications reveal subtype-specific molecular signatures and novel biomarkers. Mendelian randomization (MR) studies further reveal causal links between rosacea and autoimmune, metabolic and gastrointestinal comorbidities-that rosacea is more than skin deep. The role of the gut-skin axis, particularly involving small intestinal bacterial overgrowth (SIBO) and Helicobacter pylori infection, reflects the importance of microbial and neuroimmune crosstalk. Disparities in diagnosis and management persist, particularly among individuals with skin of colour (SOC) and those with limited healthcare access. By integrating an exposomal framework, this review advocates for a paradigm shift in rosacea management: from reactive treatment to proactive, exposome-informed intervention. Personalized skincare, microbiome-targeted strategies, dietary modulation and psychosocial support represent emerging pillars in a holistic, precision medicine framework. Future research should prioritize exposome-informed prevention, inclusive care models, and the development of personalized interventiouns that address both cutaneous and systemic facets of rosacea.
Transcutaneous auricular vagus nerve stimulation treatment for erythematotelangiectatic rosacea: a randomized clinical trial.
Li J, Wei J, Zhang M, et al. JAMA Dermatol. 2025 Oct 8. Epub ahead of print. DOI: 10.1001/jamadermatol.2025.3796. PMID: 41060641.
Importance: Treatment of facial flushing and erythema for patients with erythematotelangiectatic rosacea (ETR) is challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) therapy may be beneficial for treating ETR; however, it has not been rigorously evaluated in a randomized clinical trial. Objective: To evaluate the efficacy of taVNS for ETR compared with sham stimulation (SS). Design, setting, and participants: Enrollment for this single-center, randomized, double-blind, sham-controlled device clinical trial was initiated in February 2024 and ended in August 2024. The follow-up period ended in February 2025, and data were analyzed in March 2025. Patients with ETR that was accompanied by a Clinician's Erythema Assessment (CEA) score of at least 2 were selected from the Department of Dermatology of Southwest Hospital in China. Interventions: Patients were allocated to the taVNS group (stimulation pulses at a frequency of 30 Hz and a pulse width of 200 μs for 30 minutes per day) or the SS group at a 1:1 ratio. Both groups received 3 weeks of treatment and 24 weeks of follow-up. Main outcomes and measures: The primary outcome was CEA score after 3 weeks of treatment. The secondary outcomes included improvements in erythema and facial flushing, sleep disorders, migraine, anxiety, fatigue, and depression, as measured via clinical tools. Results: Seventy-two participants (67 female individuals [93.1%]; median [IQR] age: 29.5 [24.0-36.0] years) with ETR were randomized into either the taVNS (36 [50.0%]) or SS groups (36 [50.0%]). At 3 weeks, the mean (SD) CEA score was lower in the taVNS group than the SS group (1.56 [0.84] vs 2.47 [0.81]; mean difference, -0.92; 95% CI, -1.3 to -0.53; P < .001). Moreover, taVNS also reduced the severity of anxiety (mean difference, -5.42; 95% CI, -8.11 to -2.73; P < .001) and depression (mean difference, -6.22; 95% CI, -9.69 to -2.75; P < .001). This relief persisted until the follow-up period. The effects on sleep disorders, migraine, and fatigue were consistent with the previously described indicators. Adverse events were not common for taVNS (2 of 36 [5.6%]) and SS (3 of 36 [8.3%]). Conclusions and relevance: This randomized clinical trial demonstrated that treating ETR with taVNS concurrently ameliorated cutaneous symptoms and systemic comorbidities, and the results suggest that taVNS is a novel therapeutic option for ETR management.
Long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser alleviates rosacea by improving lymphatic vessel dysfunction.
Gu D, Pan R, Liu T, et al. Inflamm Res. 2025 Oct 22;74(1):147. DOI: 10.1007/s00011-025-02117-1. PMID: 41123652.
Objective and design: We aimed to investigate potential lymphatic vessel abnormalities associated with rosacea and elucidate effective rosacea treatment mechanism using long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser (LPND). Material or subjects: 32 female BALB/c mice were used to established the rosacea-like inflammation model and LPND treatment model. Human lymphatic endothelial cells (HLECs) were used for in vitro studies. Treatment: LL37 and/or LPND treatment. Methods: Transcriptomic analyses and clinical observation were performed. Techniques such as Western blotting, immunofluorescence staining, flow cytometry, and clearance assays were employed to assess characteristics of lymphatic vessels. Statistical comparisons between two groups were conducted using Student's t-test or the Mann-Whitney U test, while comparisons among more than two groups were analyzed using one-way or two-way analysis of variance (ANOVA). Results: Individuals with rosacea exhibited lymphatic dysfunction and LPND treatment could alleviate rosacea-associated clinical edema. Comparative analyses of acute and chronic mouse models revealed lymphatic vessel dilation, reduced density, and impaired function in chronic rosacea-like inflammation. LPND treatment mitigated chronic rosacea-like inflammation by ameliorating lymphatic vessel abnormalities. In vitro experiments demonstrated that LPND attenuated LL-37-induced inflammatory responses in HLECs. Conclusions: We elucidated the abnormalities of lymphatic vessels in rosacea and provided evidence supporting the targeted lymphatic vessel therapies.
Therapeutic effects of Q-switched 1064 nm Nd:YAG laser on rosacea in a mouse model: inflammation and angiogenesis modulation.
Shi J, Zhang YX, Ye D, et al. Lasers Surg Med. 2025 Oct 21. Epub ahead of print. DOI: 10.1002/lsm.70074. PMID: 41117074.
Objectives: Rosacea is a chronic inflammatory skin condition with a complex pathogenesis involving immune dysregulation and angiogenesis. Q-switched 1064 nm neodymium:yttrium-aluminum-garnet (QSNY) laser has been demonstrated as an effective treatment for rosacea; however, studies investigating histological changes following QSNY treatment are limited. This study aims to evaluate the therapeutic effects of QSNY and explore its underlying mechanisms. Materials and methods: A rosacea-like mouse model was established by intradermal injection of LL37 into BALB/c mice. Hematoxylin and eosin (H&E) staining, along with immunohistochemical staining for myeloperoxidase (MPO) and CD31, were performed to assess inflammation and angiogenesis. mRNA expression levels of rosacea-associated markers were analyzed using real-time quantitative PCR (RT-qPCR) on RNA extracted from skin lesions. Results: QSNY treatment significantly reduced skin erythema and inflammatory cell infiltration in a rosacea-like mouse model. The number of CD31- and MPO-positive cells were notably decreased following QSNY treatment. Additionally, the mRNA expression levels of rosacea-associated genes, including Toll-like receptor 2 (TLR2), kallikrein 5 (KLK5), cyclic adenosine monophosphate (cAMP), elevated interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF)-1, and VEGF-2 were downregulated. Conclusion: QSNY effectively mitigates the rosacea phenotype by suppressing inflammation and angiogenesis, highlighting its potential as a therapeutic strategy for rosacea.
Efficacy and effectiveness of high molecular weight non-cross-linked hyaluronic acid plus succinic acid mesotherapy in rosacea as adjunct therapy.
Leguina-Ruzzi A, Navarro A, Zambrano M. J Cosmet Dermatol. 2025 Oct;24(10):e70484. DOI: 10.1111/jocd.70484. PMID: 41039794; PMCID: PMC12491831.
Background: Rosacea is a highly prevalent dermatosis affecting 5% of the world's population. Its impact is not only physical but also psychological, as over 60% of patients with rosacea also suffer from depression, anxiety, and other psychological comorbidities. Currently, topical treatments yield low or unsatisfactory success rates, and rosacea complications such as disfigurement, burning sensation, and pain can greatly affect patients' well-being. Intra-dermotherapy with high molecular weight non-cross-linked hyaluronic acid plus succinic acid has shown anti-inflammatory, regenerative, and vascular modulatory effects. Objectives: To evaluate the efficacy and effectiveness of high molecular weight non-cross-linked hyaluronic acid (HMWNCHA) plus succinic acid (SA) mesotherapy in rosacea patients who are not responding to topical treatments. To determine the degree of improvement in general parameters such as erythema, telangiectasia, and skin laxity and hydration. To compare the cost of this treatment with that of laser therapy, a widely used modality. Methods: We performed a non-randomized, controlled interventional study, and we evaluated the results after three sessions (once monthly) as the primary endpoint of this mesotherapy, using a product containing 1.1% of high molecular weight non-cross-linked hyaluronic acid plus 1.6% succinic acid (full face, 2 mL per session, administered using the papule technique) in a group of 20 male and female patients, aged 40-45 years, Fitzpatrick skin types I-III, without comorbidities. All patients were already undergoing topical treatment with Ivermectin 1%, Metronidazole 0.75%, and photoprotection, but without good results or clear improvement, quantified as a reduction in the Investigator's Global Assessment (IGA) severity score of at least 1 point. Erythema, hydration, and facial telangiectasia were evaluated at every session for proper quantification. Our study group was compared with a control group that only continued their topical treatment, and the study lasted 4 months, with a prospective follow-up at 6 months. Results: Our results showed a reduction of 80% in the baseline erythema, an improvement of 30% in skin hydration, and a reduction of 20% in facial telangiectasia after three sessions, compared with patients who used only topical treatment. In addition, the costs were significantly lower than those of three sessions of laser therapy in a private healthcare setting. Conclusion: We demonstrated that using this acid combination in mesotherapy is an efficient, safe, and cost-effective adjunct therapy for patients already using a particular topical treatment.
The impact of sleep quality on skin color.
Xu J, Cai X, Qiao J, Fang H. Indian Dermatol Online J. 2025 Nov 1;16(6):887-893. Epub 2025 Oct 27. DOI: 10.4103/idoj.idoj_1011_24. PMID: 41143336.
Sleep plays a crucial role in regulating immune, endocrine, and skin functions. Increasing evidence suggests that sleep deprivation and circadian rhythm disruption can impact skin pigmentation by influencing melanocyte biology, hormonal balance, and inflammatory pathways. Clinical observations and molecular studies have revealed links between poor sleep and various pigmentary disorders. However, the underlying mechanisms remain incompletely understood, and the causal relationships are still under debate due to physiological confounders such as psychological stress and metabolic dysregulation. This review summarizes recent findings from experimental, clinical, and epidemiological studies on the relationship between sleep quality and skin pigmentation. Relevant literature was retrieved through PubMed and cross-referenced sources, focusing on research involving melanocyte activity, circadian genes (e.g., PER1, BMAL1), hypothalamo-pituitary axis (HPA) activation, and pigmentation-related dermatological conditions. Both human and animal studies were included. Poor sleep has been shown to alter skin parameters including melanin, hemoglobin, hydration, and trans-epidermal water loss, often through keratinocyte barrier impairment and microbiome imbalance. Disruption of the HPA leads to elevated cortisol and proinflammatory cytokines, further affecting melanogenesis. Clinically, sleep disturbances are associated with pigmentary disorders such as melasma, rosacea, floppy eyelid syndrome, and acanthosis nigricans. Obstructive sleep apnea contributes to pigmentation changes via hypoxia-induced inflammation and vascular remodeling. A newly described disorder, maturational dyschromia, may also involve habitual sleep patterns. Future research integrating wearable technology and artificial intelligence-based skin imaging may enable real-time, individualized assessment of sleep-pigmentation interactions.
Fully ablative CO2 laser therapy for rhinophyma: long-term efficacy, safety and insights from an artificial intelligence-assisted predictive model in a large cohort.
Barolet AC, Barolet D. Skin Health Dis. 2025 Jul 23;5(5):357-367. DOI: 10.1093/skinhd/vzaf042. PMID: 41035836; PMCID: PMC12480734.
Background: Rhinophyma, a progressive nasal deformity resulting from advanced rosacea, presents significant cosmetic and functional challenges. Fully ablative CO2 laser therapy is a recognized treatment modality, but data on its long-term efficacy and safety, and recurrence rates remain limited. Objectives: To assess the long-term outcomes, safety and patient satisfaction associated with fully ablative CO2 laser therapy for rhinophyma and to identify predictors of treatment success using an artificial intelligence (AI)-assisted model. Methods: A retrospective study was conducted on 152 patients with rhinophyma (grades I-III) treated with CO2 laser therapy at an outpatient clinic affiliated with McGill University. Patients were evaluated for aesthetic improvement using the Global Aesthetic Improvement Scale (GAIS), satisfaction surveys and follow-up assessments at 1, 3, 6 and 12 months post-treatment. Demographic and clinical data were analysed using descriptive statistics, logistic regression and a deep learning model to determine predictors of hypopigmentation, recurrence and patient outcomes. Results: Significant aesthetic improvement (GAIS ≥ 3) was observed in 84% of p atients, with an average satisfaction score of 2.51/3. Recurrence was rare (4%), occurring primarily in older men with grade III rhinophyma. Side effects included mild hypopigmentation (9%) and textural changes (2%). A deep learning model identified rhinophyma grade, age and Fitzpatrick phototype as key predictors of treatment outcomes. Logistic regression confirmed that advanced rhinophyma grades significantly reduced hypopigmentation risk [adjusted odds ratio (aOR) 0.43, 95% confidence interval (CI) 0.18-0.97; P = 0.041], while age significantly increased it (aOR 1.08, 95% CI 1.00-1.17, P = 0.026). Higher rhinophyma grades were also strongly associated with increased patient satisfaction (aOR 4.97, 95% CI 2.79-9.48; P < 0.001) and showed a trend toward higher recurrence risk (aOR = 6.11, 95% CI: 0.92-690.69, P = 0.064). Fitzpatrick phototype was significantly associated with patient satisfaction; decreasing Fitzpatrick phototype was associated with reduced odds of patient-reported satisfaction (aOR 0.48, 95% CI 0.25-0.87; P = 0.015). Conclusions: Fully ablative CO2 laser therapy is highly effective and safe for rhinophyma, with most patients achieving significant improvements after a single session. AI-assisted analysis provides valuable insights into predictors of success, enabling personalized treatment plans. Older patients had an 8% increased risk of hypopigmentation per year of age, while patients with severe rhinophyma were at lower risk of hypopigmentation but at higher risk of recurrence. These findings reinforce the role of CO2 laser therapy as a cornerstone treatment for rhinophyma while highlighting the utility of predictive analytics in guiding treatment strategies.
Intense pulsed light, light-emitting diode, and hydroxychloroquine in the treatment of rosacea: a clinical observation.
Zhang C, Song L. Lasers Med Sci. 2025 Oct 11;40(1):425. DOI: 10.1007/s10103-025-04696-1. PMID: 41073773; PMCID: PMC12513978.
Rosacea is a common, chronic inflammatory skin condition lacking specific treatment. This study investigates the efficacy of various photoelectric therapies in treating rosacea. 90 rosacea patients who visited the dermatology outpatient clinic of the hospital from August 2022 to November 2023 were analyzed (retrospective registration 20240425). The patients were categorized into three groups based on different treatment methods: the control group received oral hydroxychloroquine sulfate and topical recombinant bovine basic fibroblast growth factor; observation group 1 underwent intense pulsed light therapy in addition to the control group's treatment; observation group 2 received light-emitting diode therapy on top of the control group's regimen. The therapeutic effect was evaluated by physicians' subjective evaluation and patients' pruritus symptoms. The effective rates of observation group 1, observation group 2, and the control group were 73.3%, 66.7%, and 40%, respectively, with statistical significance (P < 0.05). There was no significant difference between observation group 1 and observation group 2 (P < 0.05). Additionally, there were no significant adverse reactions in any of the three groups. The comparison between observation group 1 and observation group 2 revealed that the two combined treatment methods achieved similar and positive therapeutic effects across various clinical manifestations. The effectiveness of both observation groups was found to be superior to that of drug therapy alone.
Case Reports
Unilateral peri-orbital oedema and mechanical ptosis: an unusual case presentation of rosacea.
Li SWR, Clancy N, Intzedy L, et al. Case Rep Ophthalmol. 2025 Aug 26;16(1):677-685. DOI: 10.1159/000548178. PMID: 41058755; PMCID: PMC12500299.
Introduction: Rosacea is an inflammatory skin condition that can present with varied ophthalmic manifestations. It is often overlooked by clinicians especially when unilateral in presentation leading to diagnostic delay and a resultant psychosocial impact. We aimed to present a unique case of ocular rosacea, highlighting the difficulty in therapeutic challenges and diagnoses in such rare cases. Case presentation: A 64-year-old Caucasian man presented with a 9-month history of persistent painless swelling of the right upper eyelid and secondary ptosis. His ophthalmic examination, serology, and MRI were otherwise normal besides mild meibomian gland dysfunction. Punch biopsy results were inconsistent and initially led to a misdiagnosis of benign squamous papillomata and, later, a differential diagnosis of dermatomyositis. He was trialled on appropriate management for these conditions without any benefit. Repeat histopathology was suggestive of rosacea, and given the persistence of symptoms despite multiple treatments, he was successfully managed with a right upper lid debulking biopsy transcutaneous blepharoplasty. Histopathological analysis of the debulking biopsy confirmed the diagnosis of rosacea, with additional features indicative of lymphoedema. Upon follow-up, there was resolution of lid swelling. Conclusion: Due to the non-specific nature of isolated ocular rosacea presentations, it can be easily misdiagnosed and, therefore, should always be considered as a differential diagnosis in persistent peri-orbital oedema. It can additionally pose significant therapeutic challenges for ophthalmologists, underscoring the importance of improving our understanding of ocular rosacea. Further, we have shown the effectiveness of surgical debulking in its management.
HaiTang Heji formula for moderate rosacea refractory to conventional therapies: a case report demonstrating holistic improvement in physical and psychological symptoms.
Liu X, Wang Y, Han Y, et al. Clin Cosmet Investig Dermatol. 2025 Oct 15;18:2663-2667. DOI: 10.2147/CCID.S518165. PMID: 41116863; PMCID: PMC12535717.
Rosacea is a chronic inflammatory skin disease that significantly impacts patients' quality of life. Current treatments have limitations. We report a case of moderate papulopustular rosacea effectively treated with the Chinese herbal formula HaiTang Heji. A 34-year-old Asian woman with a 3-year history of recurrent facial erythema, papules, pustules, and flushing, refractory to conventional therapies, showed significant improvement after 16 weeks of HaiTang Heji 20mL tid. Investigator Global Assessment (IGA) decreased from 3 to 1, Global Flushing Severity Scale (GFSS) from 3 to 1, anxiety scores decreased from moderate to mild levels, and depression scores decreased from mild to minimal levels. The patient tolerated the treatment well with no reported adverse effects, highlighting the potential safety of this herbal formula. Response was largely maintained at 21-week follow-up. HaiTang Heji's therapeutic mechanisms may involve anti-inflammatory, immunomodulatory, anti-angiogenic, and gut-brain-skin axis modulation. Further research is warranted to confirm its efficacy and safety as an alternative rosacea treatment.
News
Neurogenic Rosacea: Symptom on a Spectrum, Separate Clinical Subtype, or Both?
Medscape
As understanding of neurogenic rosacea’s pathophysiology evolves, signs point to its being both a manifestation of overall rosacea pathology and a distinct subtype warranting its own treatment strategy. This conundrum notwithstanding, experts told Medscape Dermatology that many dermatologists should expand their comfort level regarding effective treatments for neurogenic rosacea — particularly those that are commonly used in psychiatry.
Feel and Effect Work Together in Skin Care for Rosacea
Rosacea.org
When it comes to skin care for rosacea, patient preferences are nearly as important as whether it works, according to Dr. Cheri Frey, assistant professor of dermatology at Howard University College of Medicine, at the 2025 Science of Skin Summit in Austin, TX in September.
Broadening the Therapeutic Horizon of Topical Dapsone Beyond Acne
Dermatology Times
A new scoping review has evaluated the efficacy and safety of topical dapsone in managing mucocutaneous diseases other than acne vulgaris. Researchers identified promising results, especially in localized disease, immunosuppressed patients, and those who avoid exposure to systemic therapies.
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