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

Burning sensation and facial blood flow in rosacea patients: an exploration of an invisible symptom that cannot be overlooked.

Huang Y, Liu X, Dai Y, Jiang X. Clin Cosmet Investig Dermatol. 2026 Feb 26;19:534567. DOI: 10.2147/CCID.S534567. PMID: 41783295; PMCID: PMC12953030.

Background: Rosacea presents with visible symptoms and subjective symptoms like burning and itching; among these, burning may seriously impairs patients' quality of life. Current research has focused primarily on visible manifestations, with insufficient attention given to studying subjective symptoms such as burning. The aim of this study is to investigate the characteristics of burning, as well as the potential changes in facial blood flow of patients. Methods: A questionnaire survey and retrospective study were employed. 177 patients answered questions related to their burning sensation. Laser speckle contrast imaging was used to investigate the differences in facial blood perfusion. Results: Among 177 patients, 87.0% reported that the subtype of rosacea associated with burning was ETR, 58.8% experienced burning before their diagnosis, and the most commonly associated symptom was exacerbated erythema (85.3%). Dietary habits and behavioural practices can trigger burning. The onset of burning exhibits a certain seasonality, being most prevalent in winter (December, January, and February), and it is more likely to occur in the afternoon and during significant temperature fluctuations. Among five groups of patients matched by baseline characteristics and disease severity, four groups displayed higher facial blood perfusion in burning patients compared to non-burning patients within the same timeframe. Conclusion: Burning sensation can be influenced by specific dietary or lifestyle habits and changes in external temperature. Burning may be related to increased facial blood perfusion.

Efficacy and safety of oral DFD-29 versus doxycycline in rosacea: a systematic review and meta-analysis.

Ghanem L, Gutu CS, Mendoza-Millán DL, et al. Clin Exp Dermatol. 2026 Mar 9:llag118. Epub ahead of print. DOI: 10.1093/ced/llag118. PMID: 41802266.

Background: Rosacea is a chronic skin disorder causing facial erythema, telangiectasias, papules, and pustules. Guidelines recommend sub-antimicrobial doses, such as doxycycline 40 mg. If symptoms persist, evaluating the efficacy and safety of sub-antimicrobial minocycline may expand therapeutic options. Aim: The present systematic review and meta-analysis evaluates DFD-29 as a low-dose tetracycline alternative to treat rosacea. Methods: Our analysis included data from three RCTs sourced from PubMed, Embase, and Cochrane databases to compare the Investigator's Global Assessment (IGA) success, reduction in inflammatory lesion counts, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) in patients using DFD-29 versus modified-release doxycycline. Statistical analyses were conducted using RStudio. Results: In pooled analysis of 643 patients, DFD-29 significantly increased the likelihood of achieving a successful IGA score compared to doxycycline (OR 2.51; 95% CI 1.80 to 3.49; p < 0.001; I2 = 0%). The DFD-29 40 mg group had significantly greater reductions in IGA scores compared to the 20 mg group (p = 0.0210). The DFD-29 40 mg group also exhibited a higher reduction in inflammatory lesion counts than doxycycline (MD -4.56; 95% CI -6.18 to -2.93; p < 0.001), whereas the 20 mg group did not show significant results. There were no significant differences in TEAEs across groups (OR 0.96; 95% CI 0.55 to 1.66; p = 0.87; I2 = 0%), with only one SEA (atrial fibrillation) was reported with DFD-29. Conclusion: Our meta-analysis showed that DFD-29 at 40 mg daily, is a superior and well-tolerated alternative to modified-release doxycycline for moderate-to-severe rosacea.

Oral JAK inhibitors as a promising therapeutic strategy for refractory rosacea: a systematic review and meta-analysis.

Peng Y, Sun M, Chen J, et al. J Cosmet Dermatol. 2026 Mar;25(3):e70791. DOI: 10.1111/jocd.70791. PMID: 41796703; PMCID: PMC12968368.

Background: Rosacea is a chronic inflammatory dermatosis. While standard therapies exist, managing refractory subtypes remains a therapeutic challenge. Oral Janus kinase (JAK) inhibitors have emerged as potential alternatives, but systematic evidence is lacking. Aims: To evaluate the efficacy and safety of oral JAK inhibitors for rosacea through a systematic review and meta-analysis. Methods: A comprehensive search was conducted in five databases from inception to December 1, 2025. The primary outcome was the pooled clinical response rate. Secondary outcomes included the Investigator's Global Assessment (IGA), Clinician's Erythema Assessment (CEA), and Dermatology Life Quality Index (DLQI). Results: Eleven studies involving 57 patients were included. The overall pooled response rate was 89.9% (95% CI: 74.4%-99.4%), with low heterogeneity (I2 = 16.3%). Regarding secondary outcomes, 67.8% of patients achieved an IGA score of ≤ 1, and 74.6% achieved a CEA reduction of ≥ 2 points. DLQI score also decreased from 17.30 ± 3.80 to 10.00 ± 3.43. Adverse events were reported in 10.5% of patients. Conclusions: Oral JAK inhibitors show promising potential as a therapeutic option for refractory rosacea. However, given the small sample size and single-arm design, these findings are exploratory. Large-scale randomized controlled trials are urgently needed to validate these findings and guide stratified treatment.

Distinct diversity of skin cell populations of rhinophyma and hypertrophic scar illustrated by scRNA-seq.

Li Q, Geng L, He X, et al. Front Immunol. 2026 Mar 12;17:1703469. DOI: 10.3389/fimmu.2026.1703469. PMID: 41909715; PMCID: PMC13017343.

Introduction: The clinical manifestations and presentation of rhinophyma closely resemble those of hypertrophic scar tissue, both presenting as firm, fibrotic growths. Despite this phenotypic similarity, a critical divergence is observed following surgical intervention: the affected skin in rhinophyma can revert to its normal state without scar recurrence, a favorable outcome starkly contrasting with the behavior of hypertrophic scars. The underlying mechanisms for this phenomenon have yet to be elucidated. The aim of this study is to uncover the cellular and molecular disparities between these two pathological conditions using single-cell sequencing technology to resolve this clinical paradox. The objective of this study is to compare the single-cell transcriptomic profiles of rhinophyma and hypertrophic scar tissues to identify key cell types and molecular pathways that may account for the distinct healing fate of rhinophyma post-surgery and provide novel insights for the prevention and treatment of hypertrophic scars. Methods and results: We isolated single cells from rhinophyma and hypertrophic scar tissues and conducted transcriptomic analysis using high-throughput single-cell RNA sequencing technology. Employing bioinformatics methods, we analyzed the data to identify differentially expressed genes and cellular subpopulations. Our results indicate that epithelial cells in hypertrophic scar tissues exhibit distinct fibrotic characteristics not observed in rhinophyma tissues. Vascular structures in hypertrophic scar tissues are enveloped by a significant number of stromal cells, in contrast to the leaky vascular profiles observed in rhinophyma tissues. Furthermore, keratinocytes in hypertrophic scars display disordered proliferation, while the number of immune cells in rhinophyma is significantly higher than in hypertrophic scar tissues. Conclusion: These findings reveal fundamental differences in cellular composition and functionality between rhinophyma and hypertrophic scar tissues, the intrinsic differences in the tissue microenvironment predispose them to divergent healing trajectories following the same insult, offering new perspectives on the healing process of rhinophyma post-surgery and potentially providing molecular targets for the development of scar prevention strategies.

Laser-based therapies in rosacea: a comprehensive review of mechanisms, clinical efficacy, and future directions.

Szwach J, Szwajkowski M, Makówka J, et al. J Clin Med. 2026 Feb 26;15(5):1771. DOI: 10.3390/jcm15051771. PMID: 41827187; PMCID: PMC12986484.

Rosacea is a chronic inflammatory skin disease characterized by erythematous, papular, and pustular lesions. Treatment for rosacea is tailored to the type and severity of lesions and the individual needs of the patient. The primary therapy involves topical and systemic treatments. Laser therapy is also an effective method. This review summarizes current knowledge on the application of pulsed dye lasers (PDLs), potassium titanyl phosphate (KTP) lasers, intense pulsed light (IPL), neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers, carbon dioxide (CO2) lasers, and erbium-doped yttrium aluminum garnet (Er:YAG) lasers in the treatment of rosacea. Research confirms that the PDL remains the gold standard, demonstrating excellent clinical efficacy. The KTP and IPL lasers provide comparable outcomes, with relatively fewer adverse effects. Due to its greater depth of penetration, the Nd:YAG laser is used to treat lesions in the deeper layers of the skin. In advanced forms of rosacea, such as rhinophyma, ablative lasers, including CO2 and Er:YAG, are employed. This review summarizes the mechanisms of action, therapeutic applications, and adverse effects associated with the use of various laser types in the management of rosacea.

Tear film interferometry, meibography, and optical coherence tomography angiography for rosacea.

Capobianco M, Zeppieri M, Visalli F, et al. Diseases. 2026 Mar 12;14(3):105. DOI: 10.3390/diseases14030105. PMID: 41892006; PMCID: PMC13025564.

Background/objectives: Rosacea is a chronic inflammatory dermatosis that may involve the eye, causing surface and adnexal damage that can precede cutaneous signs. Detecting subclinical ocular changes is clinically important because early ocular surface dysfunction may be missed on routine examination yet progress to corneal complications, allowing earlier preventive management when identified. We prospectively evaluated subclinical ocular alterations in cutaneous rosacea using a combined, fully non-invasive high-tech imaging workflow-tear film interferometry, infrared meibography, and exploratory retinal optical coherence tomography angiography (OCT-A)-including patients without clinically evident ocular involvement. Methods: Sixteen patients with cutaneous rosacea (mean age 44.3 ± 11.2 years; 4 males, 12 females) were enrolled and divided into: Group 1-rosacea with clinically evident ocular involvement (n = 11); Group 2-rosacea without clinical ocular involvement (n = 5). Six age-matched healthy subjects served as controls (Group 3). All underwent LipiView II® interferometry and meibography to quantify lipid-layer thickness (LLT, nm) and meibomian gland (MG) loss score (1 = normal-4 = severe), plus retinal OCT-A (Optovue Inc., Fremont, CA, USA). ANOVA with post hoc Tukey test assessed inter-group differences. Results: OCT-A showed no significant alterations in superficial or deep retinal plexuses across groups (p > 0.05). Conversely, LLT was significantly reduced in both rosacea groups vs. controls (OD: 45.5 ± 21.4 nm and 67.4 ± 10.1 nm vs. 92.7 ± 8.2 nm; OS: 40.4 ± 15.3 nm and 66.4 ± 10.1 nm vs. 96.0 ± 6.7 nm; p < 0.001). MG score was markedly higher (worse) in rosacea (OD: 3.63 ± 0.50 and 3.20 ± 0.83 vs. 1.83 ± 0.75; OS: 3.45 ± 0.68 and 3.40 ± 0.54 vs. 1.66 ± 0.81; p < 0.001). Ocular symptoms were reported by 85% of patients yet slit-lamp examination revealed surface alterations in 58% of asymptomatic cases. Conclusions: Tear film interferometry and meibography detect early ocular surface impairment in rosacea—even in the absence of clinical signs—while retinal microvasculature appears unaffected. Routine ophthalmologic screening of all rosacea patients could enable prompt treatment of subclinical dysfunction, potentially preventing corneal complications. Retinal OCTA metrics were not significantly different in this small pilot cohort, and these negative findings should be interpreted cautiously pending larger studies.

Targeting macrophage-to-myofibroblast transition mitigates progression from inflammation to fibrosis in rosacea.

Chen C, Wang P, Cao Y, et al. Int J Biol Sci. 2026 Feb 4;22(5):2361-2382. DOI: 10.7150/ijbs.128841. PMID: 41800255; PMCID: PMC12965144.

Rosacea is a globally prevalent chronic inflammatory skin disorder that markedly impairs quality of life, yet treatment options are limited. A characteristic feature of rosacea is macrophage infiltration, whose role in disease pathogenesis remains incompletely understood beyond inflammation; here, we identify their contribution to fibrotic remodeling through macrophage-to-myofibroblast transition (MMT). Serum proteomics revealed that TGF-β1 was prominently elevated in rosacea patients. Moreover, single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and histological staining of skin biopsies demonstrated that fibrotic remodeling was already evident at inflammation-dominant stages, with macrophages progressively acquiring myofibroblast-like features through MMT. These observations were recapitulated in LL37-induced mouse models by scRNA-seq and ST, further validated by lineage tracing using Cx3cr1-GFP knock-in mice. Interestingly, macrophage depletion markedly alleviated LL37-induced fibrotic remodeling, underscoring the pathogenic role of MMT. Through integrative screening, we subsequently identified Bruceine A (BA), a natural quassinoid that suppressed fibrotic remodeling by reducing MMT and attenuating keratinocyte-driven inflammation in vivo. BA directly targeted STAT3 and interfered with its palmitoylation-dependent activation, thereby disrupting profibrotic and inflammatory signaling. Our findings establish MMT as a driver of fibrotic remodeling in rosacea, define STAT3 palmitoylation as a therapeutic target, and position BA as a dual-acting candidate for mechanism-based intervention.

Dermatological and gastrointestinal adverse reactions in ocrelizumab treated patients with multiple sclerosis: a case series.

Höpner LK, Marschall E, Schindler P, et al. Front Immunol. 2026 Mar 9;17:1753387. DOI: 10.3389/fimmu.2026.1753387. PMID: 41878428; PMCID: PMC13008033.

Background: Anti-CD20 therapies are widely used in patients with multiple sclerosis (pwMS). Recognition of rare adverse reactions to these therapies is therefore important. Objectives: To report dermatological and gastrointestinal adverse reactions in a single-center cohort of ocrelizumab treated pwMS. Methods: Retrospective analysis conducted at a multiple sclerosis outpatient clinic of Charité - Universitätsmedizin Berlin, Berlin, Germany, between March 2020 and February 2025. Results: Among 447 ocrelizumab treated pwMS, 8 (1.8%) developed dermatological adverse reactions after a median (range) of 20.5 (6-72) months following start of therapy, including lichen planus (n=2), rosacea (n=1), psoriatic arthritis (n=1), guttate psoriasis (n=1), psoriasis vulgaris (n=1), nail psoriasis (n=1) and palmoplantar psoriasis (n=1). Another 5 (1.1%) patients developed gastrointestinal adverse reactions 24 (0.25-77) months after starting therapy, including Crohn's disease (n=1), toxic colitis (n=1), lymphocytic colitis (n=1), perforated appendicitis (n=1) and acute cholecystitis (n=1). Due to these adverse reactions, ocrelizumab was stopped in 7/13 patients. At last follow-up, adverse reactions had completely improved in 4/13, incompletely improved in 6/13, and persisted in 3/13 patients. Conclusions: Clinicians should be aware of dermatological and gastrointestinal adverse reactions associated with ocrelizumab, which can develop from a few weeks up to six years after start of therapy.

Phlyctenular keratoconjunctivitis with viral triggers.

Capobianco M, Cappellani F, Visalli F, et al. World J Virol. 2026 Mar 25;15(1):117124. DOI: 10.5501/wjv.v15.i1.117124. PMID: 41884461; PMCID: PMC13010927.

Phlyctenular keratoconjunctivitis (PKC) goes beyond limbal nodules. This pediatric ocular surface condition caused by delayed-type hypersensitivity to microbial antigens. The trigger is context-dependent: Mycobacterial antigens in tuberculosis-endemic areas; staphylococcal eyelid disease and rosacea in high-income areas. Although classically bacterial-driven, virus-associated presentations like herpes simplex virus (HSV)-linked phlyctenular disease, pediatric PKC during acute coronavirus disease 2019 (COVID-19) infection, and molluscum contagiosum-driven keratoconjunctivitis suggest the same antigen-mediated pathway. Photophobia and discomfort are prevalent, and corneal involvement can cause neovascularization, scarring, amblyopia, and perforation. This minireview combines epidemiologic, clinical, and immunopathologic data to identify causes and update care. Practical takeaways: (1) Treat the antigen source (blepharitis/rosacea, chlamydia, parasites) and screen for tuberculosis when risk factors exist. Consider viral triggers when history or exam suggest HSV, recent COVID-19, or eyelid molluscum; (2) Suppress inflammation promptly with a short, carefully tapered course of topical corticosteroids; (3) Use topical cyclosporine as a steroid-sparing agent in recurrent or steroid-dependent disease; and (4) Reduce antigen load with lid hygiene and targeted antimicrobials. Start antitubercular treatment for tuberculosis. If a viral cause is anticipated, add antiviral medication or molluscum lesion eradication to the steroid-sparing regimen. Trigger-focused, steroid-sparing treatment reduces recurrences, vision-threatening consequences, and steroid exposure.

Combination therapy with oral doxycycline and intradermal botulinum toxin type A for moderate-to-severe rosacea: a randomized controlled trial.

Nguyen TT, Le DH, Vu HT, et al. Indian J Dermatol. 2026 Mar-Apr;71(2):135-141. Epub 2026 Feb 27. DOI: 10.4103/ijd.ijd_654_24. PMID: 41884736; PMCID: PMC13012760.

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.

Exploring the potential link between minoxidil use and rosacea using a real-world data base.

Vattigunta M, Kooner A, Ira S, et al. J Drugs Dermatol. 2026 Mar 1;25(3):294-295. DOI: 10.36849/JDD.9767. PMID: 41779756.

Minoxidil is a vasodilator used at higher doses as an anti-hypertensive, while low doses of oral minoxidil (LDOM) (between 0.25 and 5 mg) are effective in treating alopecia disorders. Rosacea is characterized by various subtypes, including erythematotelangiectatic, papulopustular, phymatous, and ocular. We have encountered patients with erythematotelangiectatic rosacea (ETR) who report flushing and worsening of their facial redness with use of LDOM (authors' unpublished data). To explore the association between ETR and use of LDOM, we analyzed real-world data, hypothesizing that use of vasodilatory medications like LDOM may disrupt cutaneous vascular homeostasis of ETR.

Case Reports

Case Report: Lupus miliaris disseminatus faciei successfully treated with thalidomide combined with photodynamic therapy: two cases and literature review.

Feng H, Sun Z, Li H, et al. Front Immunol. 2026 Feb 25;17:1724732. DOI: 10.3389/fimmu.2026.1724732. PMID: 41822486; PMCID: PMC12975897.

Lupus miliaris disseminatus faciei (LMDF) is a rare granulomatous rosacea characterized by multiple papular eruptions primarily affecting the central face, resulting in both physical discomfort and notable cosmetic concerns. Despite various proposed therapies, the optimal treatment for LMDF remains controversial. Photodynamic therapy (PDT) employs a photosensitizer, light source, and oxygen to generate reactive oxygen species (ROS) that selectively target and destroy abnormal tissue, and it has also been shown to reduce and prevent scar formation. However, data on PDT use in LMDF is limited. Here, we report two young male patients with LMDF presenting with multiple firm red papules on the face, both of whom had previously received four lines of treatment-including antibiotics (minocycline, doxycycline, clarithromycin), topical tacrolimus, and traditional Chinese medicine-without clinical improvement. Both patients subsequently underwent four sessions of 5-aminolevulinic acid-based PDT (5-ALA-PDT) combined with oral thalidomide. Following this combination therapy, the lesions showed marked resolution, leaving only minimal depressed scars, and no relapse occurred during a 24-month follow-up. These cases suggest that PDT combined with thalidomide may provide an effective option for refractory LMDF, with early intervention potentially minimizing scarring. Further studies and controlled trials are warranted to confirm the efficacy and safety of this therapeutic approach.

Unilateral periocular granulomatous rosacea.

Pasi S, Marzano AV, Nazzaro G. J Dermatol Case Rep. 2026 19.1: 1-4. DOI: 10.61705/jdcr.19.1.2026.1.4.

Granulomatous Rosacea (GR), first described in 1970, is thought to be a peculiar variant of rosacea thanks to the presence of granulomas at histopathological examination, although some authors sustain that it is a distinct histological variant found among most of the clinical spectrum of rosacea. GR is mostly reported in middle aged women and may present centro-facial localization. Its histology is similar to that of Periorificial Granulomatous Dermatitis (PGD), although the latter is more common in the pediatric population. We present a peculiar case of a unilateral periorbital GR. A 22-year-old male in good health conditions had a dermatological consultation, complaining of a periorbital non-itching rash on the left side of his face that had been present for a few weeks. He denied any medical history or having used any topical or oral medication prior to the eruption’s onset. At clinical examination (Figure 1) papules and pustules on an erythematous background were found on the left periorbital area, whereas the contralateral side was unaffected. Mucous membranes were uninvolved and there was no palpable lymphadenopathy. Dermoscopy examination (Figure 2) showed widespread linear vessels arranged in a polygonal network and follicular opening containing whitish-grey plugs. Histology revealed moderate acanthosis with dilation of the hair follicles infundibula with some keratin plugs. Telangiectatic vessels were visible in the dermis, together with prominent perivascular lymphoplasmacytic infiltrate and perifollicular epithelioid granulomas (Figure 3). Stains for acid-fast bacilli (i.e. Ziehl-Neelsen) were negative. No abnormalities emerged at the serological routine exams.

News

New Survey Explores the Impact of Sleep on Rosacea

Rosacea.org

Sleep quality makes a big impact on one’s health — but what about its impact on rosacea? In a recent National Rosacea Society survey, 830 rosacea patients shared their experiences with sleep—whether they get enough or not, if a good night’s sleep helps with symptoms, and more.

Topical Ivermectin Enhances KTP Laser Efficacy in Reducing Rosacea Erythema and Lesions

Dermatology Times

A randomized, evaluator-blinded split-face clinical trial evaluated whether adding topical ivermectin 1% cream enhances the efficacy of potassium–titanyl-phosphate (KTP) 532 nm laser therapy for treating facial erythema in patients with rosacea. The combination regimen was safe and well-tolerated, supporting its potential role as an adjunctive strategy in laser-based rosacea management.

Low-Dose Minocycline Hydrochloride Is Effective Regardless of Rosacea Severity

Dermatology Advisor

An oral modified low-dose formulation of minocycline hydrochloride 40 mg (DFD-29) demonstrated greater efficacy than doxycycline and placebo in adults with moderate to severe rosacea, with consistent outcomes across baseline severity groups. These study findings were presented at the American Academy of Dermatology (AAD) 2026 Annual Meeting held in Denver, Colorado from March 27 to 31.

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