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.

Research

Neurohormonal-immune dysregulation in rosacea: emerging perspectives from the skin-gut-brain axis.

Shi L, Li S, Yao X, et al. Drug Des Devel Ther. 2026 Jun 16;20:608151. DOI: 10.2147/DDDT.S608151. PMID: 42325915; PMCID: PMC13282955.

Rosacea is a chronic inflammatory skin disease with a global prevalence of approximately 5.1%. Existing evidence suggests that its pathogenesis may be associated with dysregulation of the neuro-hormone-immune network within the skin-gut-brain axis framework. This review summarizes the potential roles of stress hormones, sex hormones, and insulin-like growth factor-1 in the four major subtypes. In erythematotelangiectatic rosacea, glucocorticoid resistance within keratinocytes may induce CCL20-driven Th17 inflammation, while catecholamines released by sympathetic nerves are associated with neurovascular flushing. In papulopustular rosacea, androgen excess, relative estrogen deficiency, LL-37-mediated innate immune activation, and gut microbiota dysbiosis may collectively contribute to the formation of inflammatory skin lesions. In the phymatous type, insulin-like growth factor-1 and androgens may interact through the PI3K/Akt/mTOR and FoxO1 pathways, promoting sebaceous gland hyperplasia and fibrosis. Ocular rosacea is associated with gut-derived low-grade systemic inflammation and neurogenic inflammation. For treatment, β-receptor blockers such as carvedilol and selective serotonin reuptake inhibitors such as paroxetine can be used for erythematotelangiectatic rosacea; anti-androgen drugs like spironolactone and metformin may be explored for papulopustular rosacea; metformin for the phymatous type; and for ocular rosacea, topical corticosteroids can be used cautiously for a short term under ophthalmological supervision. Adjunctive interventions such as eradication of small intestinal bacterial overgrowth, a low glycemic index diet, and mindfulness-based stress reduction therapy also demonstrate potential.Taken together, existing evidence supports viewing rosacea as a systemic disease potentially mediated by the skin-gut-brain axis and characterized by dysregulation of the neuro-hormone-immune network. However, more high-quality randomized controlled trials and stratified studies guided by hormone-related biomarkers are currently needed to further validate its mechanisms and advance precision treatment.

The association between atopic dermatitis and rosacea: a comprehensive review from comorbidities to pathogenic mechanisms.

Zeng Y, Feng Y. Front Immunol. 2026 Jun 5;17:1837198. DOI: 10.3389/fimmu.2026.1837198. PMID: 42327780; PMCID: PMC13280930.

Objective: Atopic dermatitis (AD) and rosacea have traditionally been regarded as two distinct inflammatory skin disorders with divergent pathophysiology. However, emerging evidence has progressively revealed unexpected convergences between these conditions in clinical manifestations, comorbidity profiles and pathogenic mechanisms-raising the question of whether the apparent mechanistic overlaps represent true pathophysiological convergence — sharing common upstream drivers — or merely parallel, non-specific innate immune responses triggered by entirely distinct microbial and genetic factors? This distinction carries profound implications for the design of shared versus disease-specific therapeutic strategies. This review aims not simply to enumerate similarities but to critically evaluate whether the observed convergences represent true mechanistic overlap, or parallel but independent responses. Methods: Literature search strategy: A comprehensive literature search was conducted in PubMed, Embase and Scopus, the Cochrane Library between April, 2016 and April, 2026. The search strategy combined controlled vocabulary and free-text terms, including "rosacea", "atopic dermatitis", "mast cells", "comorbidity", "microbiome", "innate immunity", "adaptive immunity", and "neurovascular". Reference lists of relevant articles were also manually screened to identify additional eligible studies. Inclusion and exclusion criteria: Studies were included if they: (1) focused on atopic dermatitis and/or rosacea; (2) investigated relevant immunological mechanisms, comorbidities, or pathophysiological pathways; and (3) provided sufficient data to support qualitative synthesis. Both original research articles and high- quality reviews or meta-analyses were considered. Studies were excluded if they: (1) were duplicate publications; (2) lacked sufficient methodological detail or extractable data; or (3) were not directly relevant to the objectives of this review. Study selection and data extraction: Study selection and data extraction were performed independently by two reviewers. Titles and abstracts were initially screened, followed by full-text assessment for eligibility. Any discrepancies were resolved through discussion, and when necessary, a third reviewer was consulted to reach consensus. Study selection process: A total of 5381 records were identified through database searching, with an additional 83 records identified through manual reference screening. After removal of duplicates, 3185 records remained for title and abstract screening, of which 2864 were excluded due to irrelevance. A total of 321 full-text articles were assessed for eligibility, and 216 were further excluded for the following reasons: lack of relevance (n =117), insufficient data (n =53), or low methodological quality/non-original articles (n = 46). Ultimately, 105 studies were included in the qualitative synthesis. The study selection process is summarized in a PRISMA-style flow diagram (Graphical Abstract, below). Given the narrative nature of this review, no formal risk-of-bias assessment was performed. Results: Critical appraisal of the evidence reveals that both diseases share an upstream innate immune activation platform' encompassing TLR2/TLR4 signaling, NLRP3 inflammasome activation, mast cell degranulation and neurovascular dysregulation via the CGRP/SP/VEGF/TRP axis. However, they diverge at the level of adaptive immune polarization: AD is dominated by Th2/ILC2 skewing with IgE sensitization and deficient antimicrobial peptide responses, while rosacea is characterized by Th 1/Th17 involvement with autonomous LL-37 overproduction as its primary amplification loop. Intriguingly, dupilumab-induced rosacea-like dermatitis suggests that these polarization states may not merely differ but actively compete, raising questions about the nature and limits of mechanistic overlap between the two conditions. This duality may challenge simplistic models of mechanistic overlap and has direct implications for differential clinical management. Future research should employ multi-omics approaches and prospective comorbidity cohorts to clarify causal pathways and translate mechanistic insights into optimized therapeutic strategies.

The role of the vagus nerve and its stimulation in modulating inflammatory skin diseases and other dermatologic conditions: from mechanisms to therapeutics.

Nahm WJ, Falanga V, Kim KJ, et al. Dermatology. 2026 Jun 12:1-31. Epub ahead of print. DOI: 10.1159/000552415. PMID: 42287674.

Background: Inflammatory skin diseases typically exhibit autonomic imbalance characterized by sympathetic dominance and parasympathetic hypofunction. The vagus nerve plays a fundamental role in modulating inflammatory responses through the cholinergic anti-inflammatory pathway, a neural circuit in which vagal efferent signals lead to acetylcholine release that suppresses pro-inflammatory cytokine production, and hypothalamic-pituitary-adrenal axis (HPA). Summary: This review analyzes emerging evidence supporting vagus nerve stimulation (VNS) as a therapeutic approach for inflammatory skin diseases. We reviewed preclinical studies and published clinical reports examining the effects of invasive and non-invasive VNS on inflammatory skin conditions and associated biomarkers. Recent research demonstrates that VNS can reset a dysregulated HPA axis and reduces inflammatory cascades by inhibiting inflammasome activation, attenuating pro-inflammatory cytokine synthesis, and accelerating inflammation resolution. Preclinical studies show that both invasive and non-invasive VNS significantly attenuate inflammatory markers in mouse models of psoriasis, eczema, and vitiligo, despite the skin lacking direct vagal innervation. Published reports document notable improvement in seborrheic dermatitis and rosacea following transcutaneous VNS. Inflammatory skin diseases share similar comorbidity profiles with conditions directly linked to vagal dysregulation, suggesting a common pathophysiological framework defined by impaired neuroimmune communication. The "Cutaneous Vagal Dysregulation Inflammatory Axis" views inflammatory skin disorders as resulting from a bidirectional relationship in which autonomic imbalance promotes a pro-inflammatory state across multiple organ systems.

Decoding the neurological connection between rosacea and migraines: exploring shared mechanisms.

Arain A, Babar M, Martins N, Lee D. Cureus. 2026 May 11;18(5):e108668. DOI: 10.7759/cureus.108668. PMID: 42281675; PMCID: PMC13252815.

Rosacea and migraine are prevalent chronic disorders traditionally viewed as distinct conditions affecting separate organ systems. However, emerging evidence suggests a significant overlap, notably through shared neurovascular and neuroinflammatory pathways. This literature review explores the mechanisms linking rosacea, a chronic inflammatory skin condition characterized by facial flushing and sensitivity, and migraine, a neurological disorder marked by recurrent headaches. Current research highlights the critical roles of neuropeptides, including calcitonin gene-related peptide (CGRP), substance P (SP), and pituitary adenylate cyclase-activating polypeptide (PACAP), in mediating inflammation and vascular dysregulation common to both conditions. Despite these advances, notable gaps remain, such as limited data on the impact of migraine treatments (e.g., CGRP inhibitors) on rosacea, unclear reasons behind the selective comorbidity of these conditions, minimal research comparing rosacea to other headache disorders, and methodological limitations across studies. Addressing these gaps through interdisciplinary research holds promise for improved clinical outcomes. This review underscores the importance of recognizing rosacea and migraine as interrelated neurovascular disorders, advocating for integrated therapeutic approaches, and proposing directions for future research.

Formulary coverage of topical rosacea therapies in United States commercial insurance: a cross-sectional review.

Farah M, Zarabian N, Menta N, et al. J Drugs Dermatol. 2026 Jun 1;25(6):577-578. DOI: 10.36849/JDD.9790. PMID: 42235033.

To the Editor, Rosacea is a chronic inflammatory disorder primarily affecting the face, characterized by erythema, telangiectasia, inflammatory lesions, and flushing. Rosacea affects up to 10% of the global population and is associated with a reduced quality of life and higher rates of depression and anxiety compared to the general population, underscoring the importance of effective treatment.

Low-dose isotretinoin: an option for the treatment of scalp and facial rosacea.

Lillich M, Muse M, Bermudez I, et al. J Clin Aesthet Dermatol. 2026 Apr;19(4):28-29. PMID: 42239842; PMCID: PMC13229152.

Extrafacial rosacea involving the scalp is an uncommon manifestation of acne rosacea, for which evidence-based treatment guidance is limited. With this retrospective study, we aimed to evaluate the effectiveness and tolerability of low-dose isotretinoin in patients with rosacea involving both the face and scalp. We conducted an observational chart review of adult male patients treated with isotretinoin for this condition at our multisite private practice between 2012 and 2022; 21 patients met inclusion criteria. Treatment courses were short with a low dose (mean cumulative dose: 81.0 mg/kg; mean daily dose: 0.67 mg/kg/day; mean duration: 3.95 months). Complete clinical clearance of facial and scalp disease was achieved in 85.7% of patients, and treatment was well tolerated, with 95.2% of patients completing a full therapeutic course. This study suggests that low-dose, short-duration isotretinoin is a viable and effective systemic treatment option for extrafacial rosacea and may fill an important gap in the management of refractory scalp disease.

Understanding patient perspectives on rosacea: a cross-sectional analysis of the r/Rosacea forum on Reddit.

Goyal SP, Friedman A. J Drugs Dermatol. 2026 Jun 1;25(6):530-536. DOI: 10.36849/JDD.9643. PMID: 42235047.

Background: As the largest online rosacea forum, r/Rosacea, a subreddit hosted on Reddit, provides a unique opportunity to better understand the concerns of rosacea patients. Methods: Using Python software and artificial intelligence models, a total of 1,000 posts from the r/Rosacea subreddit were analyzed for emotional tone, post category, and mentions of signs and symptoms, as well as medications. Results: The majority of posts were classified as seeking advice (n = 631), and posts categorized as patient stories received the highest median upvotes (P<0.001). Rosacea patients were found to be most concerned with external appearance, with redness (45.2%) and pustules (24.2%) being the most discussed signs in advice-seeking posts. Posts referencing burning exhibited strong negative emotional tones of anger and disgust. Ivermectin (12.7%) and azelaic acid (10.9%) were the most discussed medications in advice-seeking posts, and ivermectin received significantly lower median upvotes (P=0.0067). Conclusion: The insights of this cross-sectional analysis aid in achieving a deeper understanding of the rosacea patient perspective. Additional emotional analysis of the posts highlights the need for greater focus on the psychological burden of the disease. The frequency and popularity of rosacea medications reveal potential gaps in patient education and raises concerns regarding treatment adherence to medications, including ivermectin. It is imperative to increase rosacea patient access to quality-assured educational resources and to limit the potential spread of misinformation on r/Rosacea.

Gut microbiota, metabolic markers, and systemic inflammation in young women with self-reported rosacea: an exploratory cross-sectional study.

Pavačić P, Krpan E, Zeman K, et al. J Clin Med. 2026 May 27;15(11):4130. DOI: 10.3390/jcm15114130. PMID: 42278997; PMCID: PMC13258242.

Background: Rosacea is a chronic inflammatory dermatosis with emerging links to the gut-skin axis, yet integrative data connecting fecal microbiota with metabolic and immune parameters remain scarce. Methods: Within a cohort of Croatian women (N = 300, aged 30-35), participants with self-reported physician-diagnosed rosacea (n = 19) were compared to controls (n = 281). Assessments included validated questionnaires, anthropometrics, fasting blood parameters, and fecal 16S rRNA gene sequencing (QIIME2). Taxonomic profiling at four levels (899 features) used Mann-Whitney U tests with per-level Benjamini-Hochberg FDR correction. This study follows STROBE and STORMS guidelines. Results: On the host side, rosacea was nominally associated with higher BMI (p = 0.037), poorer sleep quality (p = 0.038), elevated monocytes (p = 0.031), and higher HOMA-B (p = 0.013); these comparisons were not corrected for multiple testing. Fecal 16S rRNA analysis (rosacea n = 18, controls n = 265) identified 15 nominally significant genera, including depleted Bifidobacterium (p = 0.007), Roseburia (p = 0.033), and enriched Anaerostignum (p < 0.001). However, no taxon survived FDR correction at any taxonomic level (lowest q = 0.165), and the total number of nominally significant features (48/899, 5.3%) did not exceed chance expectation (binomial p = 0.340). All key taxa remained nominally significant after BMI adjustment. An exploratory Random Forest classifier (five genera + HOMA-B + cortisol) achieved LOOCV AUC = 0.785, but feature selection on the training data limits interpretation. Conclusions: In this narrowly age-defined female cohort, host-side metabolic and immune differences reached nominal significance without multiple-testing correction. Fecal microbiota differences were exclusively exploratory: no taxon survived FDR correction, and the overall signal did not exceed chance expectation. The pattern of findings is compatible with-but does not constitute evidence for-a gut-skin axis contribution to rosacea. Confirmation in adequately powered cohorts with clinical rosacea verification, comprehensive confounder capture, and pre-registered analyses is required before any mechanistic or clinical conclusions can be drawn.

Serum ischemia-modified albumin levels in mild to moderate rosacea: an exploratory case-control study.

Şen O, Çakmak SK, Hayran Y, Neşelioğlu S. Cutan Ocul Toxicol. 2026 Jun 23:1-9. DOI: 10.1080/15569527.2026.2692382. Epub ahead of print. PMID: 42333524.

Background: Rosacea is a chronic inflammatory dermatosis in which oxidative stress has been implicated as a pathogenic factor. Ischemia-modified albumin (IMA) is a serum biomarker of oxidative stress not previously evaluated in rosacea. Objective: To explore serum IMA levels in rosacea patients versus healthy controls and examine associations with disease severity and clinical characteristics. Methods: In this exploratory case-control study, 72 rosacea patients and 72 age- and sex-matched healthy controls were enrolled. Serum IMA was measured by the albumin cobalt-binding (ACB) colorimetric method with concurrent serum albumin measurement. Statistical analysis included between-group comparisons, Benjamini-Hochberg false discovery rate (FDR) correction, and multivariable linear regression. Results: Mean serum IMA did not differ significantly between rosacea patients (0.72 ± 0.19 ABSU) and controls (0.74 ± 0.14 ABSU; mean difference -0.02 ABSU, 95% CI [-0.08, +0.04]; Cohen's d = 0.12; p = 0.32). Serum albumin was also comparable between groups (p = 0.50). Male patients showed higher IMA than females (0.81 ± 0.13 vs. 0.72 ± 0.17 ABSU; mean difference +0.09 ABSU, 95% CI [+0.01, +0.17]; Cohen's d = 0.55; p = 0.015). A weak positive correlation between persistent erythema severity and IMA was observed (Spearman's r = 0.24, 95% CI [+0.01, +0.45]; p = 0.045), which did not retain significance after FDR correction (p = 0.058). Multivariable regression revealed no independent predictor of IMA. Conclusion: Serum IMA was not significantly elevated in rosacea. Exploratory findings suggest possible associations with male sex and erythema severity, warranting confirmation in larger phenotype-stratified studies.

Case Reports

Recurrent red eye misdiagnosed as conjunctivitis: ocular rosacea with corneal neovascularization in a young patient.

Ferreira J, Embalo A, Rodrigues A, et al. Cureus. 2026 May 11;18(5):e108670. DOI: 10.7759/cureus.108670. PMID: 42281673; PMCID: PMC13252810.

Chronic red eye is a prevalent presentation in both primary care and emergency settings. While most cases are self-limiting, recurrent or treatment-resistant episodes warrant systematic evaluation to exclude underlying chronic inflammatory conditions. We report the case of a 19-year-old female patient with a longstanding history of bilateral red eye associated with pain, photophobia, and epiphora, initially and repeatedly managed as infectious conjunctivitis in the emergency department (ED). Despite multiple antibiotic courses, symptoms persisted. Ophthalmologic evaluation ultimately revealed chronic anterior and posterior blepharitis with meibomian gland dysfunction, peripheral corneal infiltrates, and neovascularization (NV) - findings consistent with ocular rosacea. Notably, subtle cutaneous signs of rosacea were also identified on clinical examination, further supporting the diagnosis. Following targeted therapy with oral doxycycline 100 mg twice daily, topical corticosteroids (CSs), and ocular lubricants, the patient achieved significant clinical improvement. This case highlights the diagnostic pitfalls of recurrent red eye in primary care, the importance of recognizing chronic inflammatory ocular surface disease, and the value of timely ophthalmologic referral in preventing irreversible corneal complications.

Efficacy of salicylic acid chemical peeling in treating a case of severe Demodex folliculorum-induced rosacea.

Li Y, Liu X, Wang G, Jiang X. JAAD Case Rep. 2026 Apr 30;73:21-24. DOI: 10.1016/j.jdcr.2026.04.049. PMID: 42282931; PMCID: PMC13251507.

Conventional therapies are sometimes insufficient for Demodex-associated rosacea, particularly in refractory cases. In recent years, salicylic acid peeling has been increasingly used in dermatologic practice due to its keratolytic, antibacterial and anti-inflammatory properties. However, few reports exist on its efficacy specifically for rosacea with severe demodicosis. We present a recalcitrant case of rosacea complicated by heavy Demodex infestation, successfully managed with salicylic acid peeling. Dynamic reflectance confocal microscopy (RCM) observation provided in vivo visualization of mite clearance. This may offer reference for diagnosing and treating similar patients.

Successful treatment of dupilumab-induced rosacea with upadacitinib in a patient with atopic dermatitis.

Temiz SA, Abdelmaksoud A, İlgenli HE, et al. Acta Dermatovenerol Alp Pannonica Adriat. 2026 Jun;35(2):135-137. PMID: 42241636. PDF.

Dear editor, Atopic dermatitis is a chronic inflammatory disease caused by environmental and genetic factors. The leading symptom is pruritus. Rosacea is also accompanied by disturbed epidermal barrier function and dry skin.

News

What Dermatologists Say Are the Biggest Barriers to Adherence

Rosacea.org

Dermatologists presenting at the American Academy of Dermatology annual meeting in March discussed what they see as the biggest reasons acne and rosacea patients don’t stick with their prescribed treatments.

Tips for Calming Rosacea-Prone Skin in the Treatment Room

American Spa

Rosacea is one of the most common, yet often misunderstood, skin conditions among adults aged 30 to 60. In fact, an estimated 16 million Americans have rosacea, but only a fraction are being treated for the disorder, according to the National Rosacea Society (NRS). Persistent redness and flushing, bumps and pimples, and visible blood vessels on the face are just a few of the primary symptoms of rosacea, signs that can be misdiagnosed as other conditions.

Novel Botanical Moisturizer Demonstrates Superior Efficacy Over Metronidazole in Phase 2 Rosacea Trial

Dermatology Times

A novel plant-based topical moisturizer containing oat kernel oil and aloe vera demonstrated greater improvements in facial erythema and inflammatory lesions than 0.75% metronidazole cream in adults with rosacea, according to results from a randomized, double-blind controlled trial published in the Journal of Cosmetic Dermatology. The findings were highlighted in a recent press release from Crescel, the developer of the investigational product.

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