Rosacea Research Digest - December 31, 2024
This edition highlights rosacea research and marks the last free issue before subscription access begins.
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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Subscriptions are included as part of professional membership in the NRS, and are also available to all healthcare professionals, patients and others interested in this common but often misunderstood disorder affecting more than 16 million Americans.
Research
Impaired angiogenesis and Th1/Th17 polarization: a possible explanation for the decreased incidence of rosacea in the aged.
Long J, Deng Z, Chen M, Liu T. Immun Inflamm Dis. 2024 Dec;12(12):e70108. doi:10.1002/iid3.70108
Background: Rosacea is a common inflammatory skin disorder characterized by frequent facial flushing, erythema, telangiectasia, and papules, with a higher incidence observed in individuals aged 30-50 years and a tendency to decrease in the elderly. This age-related decline in incidence drew our attention to further explore the relationship between rosacea pathogenesis and aging. Methods: We analyzed the incidence of rosacea across 8340 individuals without systemic diseases. The effects of LL37-induced rosacea-like erythema and inflammation were evaluated in both young and aged mice. Immunofluorescence analysis was performed to assess microvessel density, whereas the expression levels of angiogenesis-related factors, including matrix metalloproteinases (MMPs) and vascular endothelial growth factor α (VEGFα), were quantified. Additionally, immune responses were assessed at both the cellular and systemic levels. Results: Aged mice displayed milder LL37-induced rosacea-like erythema and inflammation compared to their young counterparts. Immunofluorescence analysis revealed a decrease in microvessel density in rosacea models of the aged group. The expression of angiogenesis-related factors, including MMPs and VEGFα, was decreased in aged mice compared to young mice, indicating a reduced responsiveness to LL37 stimulation. Furthermore, we found that suppressed Th1- and Th17-polarized immune responses, one of the major pathogenic mechanisms of rosacea, were reduced in aged mice in response to LL37 stimulation at both cellular and systemic levels. Conclusion: The findings suggest that impaired angiogenesis and attenuated Th1/Th17 immune responses underlie the age-related decline in rosacea incidence.
Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation.
Zhang YR, Keshari S, Kurihara K, et al. Sci Transl Med. 2024 Dec 11;16(777):eadq9133. Epub 2024 Dec 11. doi:10.1126/scitranslmed.adq9133
Activation of dermal mast cells through the Mas-related G protein-coupled receptor B2 receptor (MrgprB2 in mice and MrgprX2 in humans) is a key component of numerous inflammatory skin diseases, including dermatitis and rosacea. Sensory neurons actively suppress mast cell activation through the regulated release of glutamate, resulting in reduced expression of Mrgprb2 as well as genes associated with proteins found in mast cell granules. To determine whether exogenous glutamate receptor agonism could suppress mast cell function, we determined that mast cells have relatively selective expression of the glutamate receptor ionotropic, kainate 2 (GluK2). A GluK2-specific agonist, SYM2081, effectively inhibited mast cell degranulation in response to MrgprB2 agonism in both murine mast cells and human skin explants in vitro as well as in vivo after both intradermal and topical administration of SYM2081 to mice. Analyses of transcriptomic datasets from SYM2081-treated mast cells using standard differential expression approaches and an interpretable machine learning technique revealed a previously unrecognized cellular program coordinately regulated by GluK2 agonism. GluK2 agonism suppressed the expression of Mrgprb2 and genes associated with mast cell proliferation. Suppression of mast cell proliferation by SYM2081 exposure was confirmed on the basis of reduced Ki-67 expression and BrdU incorporation in vitro and in vivo. Last, pretreatment with SYM2081 reduced skin inflammation in murine models of dermatitis and rosacea. Thus, agonism of GluK2 represents a promising approach to suppress mast cell activation and may prove beneficial as therapy for inflammatory diseases in which mast cell activation is pathogenic.
Efficacy of treatments in reducing facial erythema in rosacea: a systematic review.
Hua NJ, Chen J, Geng RSQ, et al. J Cutan Med Surg. 2024 Oct 31:12034754241287546. Epub ahead of print. doi:10.1177/12034754241287546
Rosacea is a chronic inflammatory skin condition that affects over 5% of individuals worldwide. Its clinical presentation is characterized by an array of features, including erythema, papules and pustules, phymatous changes, telangiectasia, and ocular manifestations. Specifically, the multifaceted manifestation of erythema varies widely in intensity and distribution. Factors contributing to pathogenesis include neurovascular dysregulation, increased levels of pro-inflammatory mediators, and aberrant vasodilation. Erythema management plays an important role in reducing the psychosocial burden associated with rosacea and improving overall quality of life. Cochrane CENTRAL, Medline, and Embase databases were searched from inception to September 2023 and included 33 clinical trials reporting on a total of 7411 rosacea patients (74.1% female) and 21 different topical or systemic treatments. The mean age was 48.8 years (range, 18-83 years), and the mean time to outcome assessment was 8.1 weeks (standard deviation, 4.1 weeks). Treatment efficacy was assessed by outcome measures including percent improvement from baseline on 4- and 5-point scales, clinician erythema assessment (CEA) success (improvement ≥1 point), and CEA and patient self-assessment success (improvement ≥1 point). Pooled effect sizes for each treatment were calculated as a weighted average based on the number of patients in each study. The most effective topical treatments for reducing erythema include sodium sulphacetamide and sulphur, praziquantel, metronidazole, and B244 spray (Nitrosomonas eutropha). The most effective systemic treatment was paroxetine. Our findings highlight the varying efficacy of treatments in addressing the erythema in rosacea, recognizing the nuances of clinical presentations.
Assessment of depressive and anxiety symptoms and health-related quality of life in rosacea patients: a case-control study.
Seetan K, Gablan M, Alnaimi M, et al. Dermatol Res Pract. 2024 Dec 7;2024:5532532. doi:10.1155/drp/5532532
Background: Rosacea, a chronic facial dermatosis, poses a substantial global prevalence burden. Its impact extends beyond physical symptoms, affecting patient quality of life, self-esteem, and psychosocial functioning. This study aims to assess the health-related quality of life and emotional well-being in Jordanian rosacea patients in comparison to healthy controls. Methods: A case-control study, matching for age and sex, was conducted among rosacea patients attending the outpatient department at a governmental secondary hospital in the north of Jordan between September 2022 and November 2023. Adult patients with a confirmed rosacea diagnosis for a duration of ≥ 3 months were paired with healthy controls. Health-related quality of life, anxiety, and depression were evaluated using the Dermatology Life Quality Index (DLQI) and the Hospital Anxiety and Depression Scale (HADS), respectively. Disease severity was assessed using the Clinician's Erythema Assessment (CEA) grading system. Results: The study included 198 rosacea patients and 198 healthy controls. Rosacea patients exhibited significantly higher DLQI scores (mean 11.32 ± 5.4) compared to controls (mean 4.28 ± 2.3), indicating diminished quality of life. Subscale analysis revealed prominent differences in symptoms/feelings and daily activities. Additionally, rosacea patients reported elevated scores on the HADS anxiety (mean 9.38 ± 3.2) and depression (mean 8.19 ± 4.3) subscales in contrast to controls (mean 3.88 ± 2.18 and mean 3.41 ± 1.87, respectively). More than half (57%) of rosacea patients experienced moderate or severe anxiety, and nearly a third (31%) reported moderate or severe depression. Regression analyses revealed that higher disease severity significantly predicted worse quality of life (β = 0.384), anxiety (β = 0.352), and depression (β = 0.312). Conclusion: The study demonstrated that rosacea patients in Jordan experience significantly diminished quality of life and higher rates of anxiety and depression compared to healthy controls. Disease severity and multiple facial lesions emerged as strong predictors of poor psychological outcomes, while female gender increased vulnerability and longer disease duration showed a protective effect. These findings emphasize the need for routine psychological screening and a holistic treatment approach, particularly for newly diagnosed patients with severe disease manifestations.
Effects of botulinum toxin type A treatment on clinical and biophysical parameters in patients with erythematotelangiectatic rosacea: a prospective, randomized, controlled, double-blind study.
Dağtaş BB, Erdem O, Güneç Tİ, et al. Dermatol Surg. 2024 Dec 16. Epub ahead of print. doi:10.1097/DSS.0000000000004528
Background: Erythematotelangiectatic rosacea (ETR) lacks a gold-standard treatment. Recent studies show that intradermal Botulinum Toxin-A (BoNT-A) is effective for erythema, though objective data are limited. Objective: This study aims to evaluate the efficacy and tolerability of intradermal BoNT-A in patients with ETR. Methods: In this randomized, double-blind, split-face study, 30 patients were enrolled. One side of the face received 15 units of BoNT-A, reconstituted in 10 mL of saline, while the control side received saline injections. Assessments were made at baseline and 1-month posttreatment. Clinician's Erythema Assessment (CEA) scale and Patient Self-Assessment (PSA) scores were recorded. Erythema and Melanin Index measurements using a Mexameter. Background erythema was assessed through dermatoscopy, while vascular structure and density were evaluated using Investigative Global Assessment (IGA) scores through videocapillaroscopy. Results: The BoNT-A-treated side demonstrated significant reductions in CEA scores, Erythema Index, and dermatoscopic background erythema, while no significant changes were observed on the saline control side. IGA scores indicated a significant response to treatment on the BoNT-A side. Patient Self-Assessment scores improved on both sides. No serious adverse events requiring hospitalization were reported. Conclusion: Intradermal BoNT-A effectively reduces erythema and vascular density in patients with ETR and is well-tolerated.
Rhinophyma treatment: An observational study comparing the results of the cold blade technique and ablative fractional CO2-laser.
Amiri SV, Laustsen-Kiel CM, Carlsen B, et al. J Plast Reconstr Aesthet Surg. 2024 Nov 29;101:90-96. Epub ahead of print. doi:10.1016/j.bjps.2024.11.053
Experts have widely discussed rhinophyma treatment, proposing and testing various therapies over the years. The aim of this retrospective study was to compare the aesthetic outcomes of patients undergoing the cold blade technique at the Department of Plastic Surgery and ablative fractional carbon dioxide (CO2) laser treatment at the Department of Dermatology at Zealand University Hospital. We assessed rhinophyma severity using the RHISI scale with pre-and post-operative photographs evaluated by senior consultants from each department, who were blinded to the treatment method. Additionally, the patients completed a questionnaire to gauge their satisfaction and willingness to recommend the procedure. Cosmetic outcomes were deemed excellent or good (75% for surgery and 71% for CO2-laser) in both treatment methods. Only one patient answered with moderate satisfaction. Therefore, we recommend both methods as possible treatment options.
Upgrading skin barrier protection: addition of active ingredients to a gelatin/tannic acid-based hydrogel patch for treating skin lesions related to personal protective equipment.
Graça A, Pereira C, Martins AM, et al. Int J Pharm. 2024 Dec 19;669:125110. Epub ahead of print. doi:10.1016/j.ijpharm.2024.125110
Prolonged use of Personal Protective Equipment, like surgical masks, can cause skin issues such as acne ("maskne") and rosacea flare-ups due to pressure and moisture. While dressings can protect the skin, they often reduce mask effectiveness and lack pharmaceuticals to treat common skin lesions. This study introduces an innovative dual-function gelatin/tannic acid-based hydrogel patch incorporating metronidazole (1% w/w) or salicylic acid (2% w/w) to offer both skin protection and treatment. The hydrogels were characterized for gelation temperature, burst strength, extensibility, adhesivity, and tribological properties to assess the effects of the active ingredients on their mechanical performance. In vitro release studies using Franz diffusion cells under occlusive conditions evaluated the drug release profile from the patches. Results showed that gelatin/tannic acid and gelatin/tannic acid-metronidazole hydrogels had similar gelation temperatures (41.65 ± 1.95 °C), while the salicylic acid formulation exhibited a lower gelation temperature (33.24 ± 0.40 °C). Adhesivity improved with the addition of active ingredients, increasing by about 0.5 N, and burst strength significantly increased with metronidazole (about 6 N). Both formulations demonstrated enhanced extensibility and were suitable for all skin types in tribological studies. The in vitro release studies showed an initial burst release followed by controlled release, unaffected by mask placement. These findings suggest that dual-function hydrogel patches could provide effective skin protection and improve skin health during prolonged mask use, offering a promising solution for conditions like "maskne" and rosacea.
Topographical variations in the skin barrier and their role in disease pathogenesis.
Dajnoki Z, Kapitány A, Eyerich K, et al. J Eur Acad Dermatol Venereol. 2024 Nov 28. Epub ahead of print. doi:10.1111/jdv.20463
The skin barrier can be divided into at least four functional units: chemical, microbial, physical and immunological barriers. The chemical and microbial barriers have previously been shown to exhibit different characteristics in topographically distinct skin regions. There is increasing evidence that the physical and immunological barriers also show marked variability in different areas of the skin. Here, we review recent data on the topographical variations of skin barrier components, the contribution of these variations to the homeostatic function of the skin and their impact on the pathogenesis of specific immune-mediated skin diseases (such as atopic dermatitis and papulopustular rosacea). Recognition of these topographical barrier differences will improve our understanding of skin homeostasis and disease pathogenesis and provide a basis for body site-specific targeted therapies.
Evaluation of Helicobacter pylori and small intestinal bacterial overgrowth in subjects with rosacea.
Nelson JM, Rizzo JM, Greene RK, et al. Cureus. 2024 Oct 25;16(10):e72363. doi:10.7759/cureus.72363
Background: Systemic abnormalities in the immune system may contribute to rosacea pathogenesis. Several studies have found a higher prevalence of abnormal bacterial growth, such as Helicobacter pylori (H. pylori) and small intestinal bacterial overgrowth (SIBO) in rosacea subjects. However, discrepancies remain in the literature, likely perpetuated by inconsistent testing methods and incomplete controlling for potential confounders. Objective: We aimed to evaluate the prevalence of H. pylori and SIBO in rosacea subjects after controlling for several potential confounders. Methods: This cross-sectional study evaluated subjects with papulopustular or erythematotelangiectatic rosacea. Subjects with previous or existing gastrointestinal (GI) disease, GI surgery, autoimmune disorders, immunosuppression, or significant comorbidities were excluded. Certain medication use (antibiotics, steroids, GI-modulating medications, anti-inflammatories) required an appropriate washout period. Rosacea history and severity were assessed. Subjects answered questions regarding their rosacea and GI health. H. pylori and SIBO were evaluated by 13C-urea breath test and glucose-breath test methods, respectively. Results: Of 27 subjects, 14.8% (N=4) tested positive for H. pylori and 33.3% (N=9) tested positive for SIBO. Compared to the general population prevalence, the proportion of H. pylori in the rosacea cohort was significantly less (p=0.02). Though the estimated population prevalence of SIBO had a wider range, compared to midrange, the prevalence of SIBO in the rosacea cohort was greater (p<0.001). There were no significant associations between demographics, rosacea characteristics, or GI symptoms and H. pylori or SIBO positivity. Conclusion: When eliminating several potential confounders, SIBO is more prevalent in subjects with rosacea compared to the general population. Thus, SIBO may be associated with rosacea, though it remains incompletely understood whether SIBO itself contributes to rosacea pathophysiology or rather SIBO prevalence and rosacea are both downstream effects of abnormalities in systemic immunity. Future studies are warranted to elucidate this relationship further, though this observed association may be promising for novel therapeutic targets in rosacea treatment.
Case Reports
Resolution of treatment-refractory papulopustular rosacea with vombined light source photodynamic therapy using pre-incubation nonablative fractionated laser resurfacing.
Mathew MA, Verma KK, Friedmann D, et al. Cureus. 2024 Nov 26;16(11):e74502. doi:10.7759/cureus.74502
Papulopustular rosacea is an inflammatory subtype of rosacea that can significantly impair patients' quality of life. Available treatment options range from anti-inflammatory topical and oral medications to laser and light therapies. Photodynamic therapy with aminolevulinic acid (ALA-PDT) has emerged as a more recent treatment option for papulopustular rosacea. ALA-PDT can significantly reduce the inflammatory component of rosacea, and pre-incubation nonablative fractionated laser resurfacing (NAFR) may enhance transcutaneous delivery of topical ALA. We present a case in which treatment-refractory papulopustular rosacea of 10-year duration was resolved with ALA-PDT using pre-incubation NAFR. This case highlights a novel, alternative approach to rosacea treatment that may be useful for patients recalcitrant to more conventional therapies.
Ultrasound-guided stellate ganglion block combined with pharmacological treatment for rosacea: a report of two cases.
Gao C, Wang F, Zhou L, et al. Patient Prefer Adherence. 2024 Dec 24;18:2657-2666. doi:10.2147/PPA.S484601
Rosacea is a chronic inflammatory disease primarily affecting the central facial region, significantly involving the facial blood vessels and the sebaceous gland units associated with hair follicles. The stellate ganglion block (SGB) technique can restore balance to autonomic nervous function by interrupting the impulse conduction of preganglionic and postganglionic sympathetic nerve fibers, thereby alleviating excessive peripheral blood vessel contraction, enhancing tissue blood supply, balancing hormone secretion, and modulating immune responses. SGB has demonstrated remarkable efficacy in treating various skin conditions affecting the head, face, and neck. In our case study, two patients with a disease duration exceeding six months underwent treatment involving oral medications, topical applications, and local cold spray, which yielded unsatisfactory results. Subsequently, our department employed the SGB method guided by multiple ultrasound assessments, resulting in nearly complete resolution of the intractable rosacea lesions in both patients.
News
How to Calm Rosacea-Related Facial Erythema, Flushing
Medscape
When patients with rosacea consult Julie C. Harper, MD, about persistent facial erythema, she often recommends brimonidine 0.33% gel or oxymetazoline 1% cream.
Hormonal IUDs May Increase Risk of Rosacea
Rosacea.org
Women who use certain hormone-releasing intrauterine devices (IUDs) may be at increased risk of developing rosacea, according to a research letter published in the Journal of the American Academy of Dermatology.
New findings might help treat rosacea, other skin issues
UPI/HealthDay News
It's still early science – studies in mice and in human cells – but researchers are on the trail of an effective new treatment for inflammatory skin conditions such as rosacea.
National Rosacea Society Introduces New Informational Postcard
Rosacea.org
The National Rosacea Society has introduced a new informational postcard about rosacea, a chronic facial skin disorder that affects more than 16 million Americans. The postcard, titled “Rosacea: A Common Disease, Uncommonly Treated,” is intended for dermatologists and other health professionals to educate new rosacea patients about the disease, and includes information about signs and symptoms, management tips and the handy CAMP mnemonic device to help patients remember the proper order of steps in their daily care routine.
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