Rosacea Research Digest - August 30, 2024
The Rosacea Research Digest from the National Rosacea Society keeps you up to date on news, reviews, presentations, and recently published basic and clinical research on rosacea. It goes out on the last weekday of each month.
The Rosacea Research Digest from the National Rosacea Society keeps you up to date on news, reviews, presentations, and recently published basic and clinical research on rosacea. It goes out on the last weekday of each month.
Subscriptions are included as part of professional membership in the NRS, and are also available — free for a limited time — to all healthcare professionals, patients and others interested in this common but often misunderstood disorder affecting more than 16 million Americans.
We appreciate your feedback as we develop this new resource. Please email us at digest@rosacea.org with your comments and suggestions.
Research
Health-related Quality of Life of Patients with Rosacea: A Systematic Review and Meta-analysis of Real-world Data.
Chiu CW, Tsai J, Huang YC. Acta Derm Venereol. 2024 Jun 25;104:adv40053. doi:10.2340/actadv.v104.40053
Patients with rosacea commonly experience stigmatization, which induces stress and thereby exacerbates their symptoms. Given the strong effects of rosacea on health-related quality of life (HRQoL), addressing the physical and psychosocial aspects of rosacea is essential. To examine the effects of rosacea on HRQoL, we conducted a systematic review and meta-analysis involving real-world data. PubMed, EMBASE, and the Cochrane Library were searched, and randomized controlled trials (RCTs), cross-sectional studies, and case series evaluating the HRQoL of patients with rosacea were included. HRQoL assessment tools such as the Dermatology Life Quality Index (DLQI) and Rosacea-Specific Quality-of-Life Questionnaire (RosaQoL) were used. Data on 13,453 patients were retrieved from 52 eligible studies: 4 RCTs, 15 case series, and 33 cross-sectional studies. Compared with healthy controls, patients with rosacea had significantly lower DLQI scores (standardized mean difference [SMD] = -1.09, 95% confidence interval [CI] = -0.81 to -1.37). The DLQI scores after treatment were higher than those before treatment (SMD = -1.451, 95% CI = -1.091 to -1.810). The pooled estimates for the overall DLQI and RosaQoL scores were 8.61 and 3.06, respectively. In conclusion, patients with rosacea have lower HRQoL compared with healthy individuals, and treatment for rosacea improves their HRQoL.
Therapeutic strategies focusing on immune dysregulation and neuroinflammation in rosacea.
Tu KY, Jung CJ, Shih YH, Chang ALS. Front Immunol. 2024 Jul 29;15:1403798. doi:10.3389/fimmu.2024.1403798
Rosacea is a complex inflammatory condition characterized by papulopustular lesions and erythema on the central face for which there is no cure. The development of rosacea is influenced by both external triggers and genetics, but the common pathophysiology is overactivation of the immune system. Here, we review the current data on proinflammatory cytokines and dysregulation of the neurovascular system as targetable components of rosacea. Amelioration of cutaneous and gastrointestinal dysbiosis and other external factors impacts the immune state and has been observed to improve rosacea. While multiple treatments exist, many patients do not achieve their goals for rosacea control and highlights an unmet need for dermatologic care. Current interventions encompass topical/oral drugs, light devices, and avoidance of triggers management. Additional understanding of the underlying pathogenesis may help us develop novel targeted therapeutic strategies to improve rosacea.
Drug-induced rosacea: A systemic review
Rijal H, Geng R, Wilken B, et al. J Cutan Med Surg. 2024 Jul 29:12034754241265719. Epub ahead of print. doi:10.1177/12034754241265719
Rosacea is a common, chronic inflammatory skin condition characterized by a heterogenous mix of features including erythema, papules, pustules, phymatous changes, telangiectasias, and ocular manifestations. Onset of rosacea thought to be triggered by systemic or topical drug therapy have been documented, but summary evidence is lacking. We performed a systematic review to collate characteristics of reported cases of drug-induced rosacea.
Rosacea in East Asian populations: Clinical manifestations and pathophysiological perspectives for accurate diagnosis.
Nobeyama Y. J Dermatol. 2024 Aug 10. Epub ahead of print. doi:10.1111/1346-8138.17411
Rosacea is a chronic inflammatory disorder primarily affecting the facial skin, prominently involving the cheeks, nose, chin, forehead, and periorbital area. Cutaneous manifestations encompass persistent facial erythema, phymas, papules, pustules, telangiectasia, and flushing. The pathogenesis of rosacea is associated with various exacerbating or triggering factors, including microbial infestation, temperature fluctuations, sunlight exposure, physical exertion, emotional stress, consumption of hot beverages and spicy foods, and exposure to airborne pollen. These environmental factors interact with genetic predispositions in the development of rosacea. The roles of the lipophilic microbiome, ultraviolet radiation, nociceptive responses, and vascular alterations have been proposed as significant factors in the pathogenesis. These insights contribute to understanding the anatomical specificity of facial involvement and the progressive nature of rosacea. East Asian skin, predominantly classified as Fitzpatrick skin phototypes III to IV, is characterized by relatively diminished skin barrier function and increased sensitivity to irritants. Airborne pollen exposure may particularly act as a trigger in East Asian individuals, possibly mediated through toll-like receptors. The lack of specificity in objective clinical and histopathological findings leads to diagnostic challenges for individuals with colored skin, including East Asians, particularly when erythema is the sole objective manifestation. An alternative diagnostic scheme may thus be necessary. A diagnostic approach emphasizing vascular manifestations and nociceptive symptoms potentially holds promise for individuals with darker skin tones. More research focusing on potential variations in skin physiology across different racial groups is essential to establish more effective diagnostic schemes applicable to both dark and light skin colors.
Effect of topical microencapsulated benzoyl peroxide on the skin microbiome in rosacea: A randomized, double-blind, crossover, vehicle-controlled clinical trial.
Nong Y, Sugarman J, York JP, et al. J Clin Aesthet Dermatol. 2024 Aug;17(8):19-26. PMID: 39148964 PMCID: PMC11324191
Objective: We sought to evaluate changes in microbiome biodiversity and physical properties of the skin after eight weeks of once-daily topical microencapsulated benzoyl peroxide (E-BPO) compared to vehicle cream in participants with rosacea.
Methods: This was a randomized, double-blind, crossover, single-center, vehicle-controlled evaluation of E-BPO on the skin microbiome in rosacea. Participants had facial rosacea with global severity of 3 or 4 on the Investigator Global Assessment (IGA) scale. In the Treatment 1-2 group, participants received E-BPO for eight weeks then switched to vehicle cream for four weeks. In the Treatment 2-1 group, participants received vehicle cream for eight weeks, then E-BPO for four weeks.
Results: Thirty-one participants were enrolled and randomly assigned to either group. Demographic characteristics were comparable between the treatment groups. After eight weeks of E-BPO treatment, there was a marked reduction in the relative abundance of Staphylococcus accompanied by an increase in Cutibacterium. At the species level, there was an increase in the relative abundance of C. acnes and a decrease in abundance of S. epidermidis. No noticeable difference was detected at the genus or species level at Week 8 in the 2-1 group. Sebum level, IGA, lesion counts, facial erythema, and inflammatory scores were improved with E-BPO versus vehicle cream. Adverse events were mild or moderate in severity.
Limitations: The study included a small number of subjects and only surface-swabs were used for microbiome sampling.
Conclusion: E-BPO shifted the skin microbiome in rosacea and demonstrated improvements in clinical symptoms and skin physical properties and a well-tolerated safety profile.
Association between Air Quality Index and the risk of rosacea: A nationwide population-based cohort study.
Ma SH, Wu CY, Li MC, et al. Clin Exp Dermatol. 2024 Jul 27:llae291. Epub ahead of print. doi:10.1093/ced/llae291
Background: Air pollution is associated with several inflammatory skin disorders. However, the association between air quality and rosacea remains unclear.
Objective: To investigate the association between air quality index and incidence of rosacea.
Methods: Overall, 21,709,479 participants without rosacea before 2008 were recruited from the Taiwan National Health Insurance Research Database. The long-term average air quality index (AQI) value for each participant was acquired from the Taiwan Air Quality Monitoring System Network and calculated from 2008/1/1 until the diagnosis of rosacea, withdrawal from the National Health Insurance, or December 31, 2018.
Results: We observed a significant association between AQI and the incidence of rosacea, with each unit elevation in AQI increasing the risk of rosacea by 5 %. Compared with the Q1 group, the Q2, Q3, and Q4 cohorts exhibited 1.82-fold, 4.48-fold and 7.22-fold increased risk of rosacea, respectively. Additionally, exposure to PM2.5, SO2 and CO increased the risk of rosacea, whereas exposure to PM10 was associated with a lower risk.
Conclusion: This study supported a significant dose-response relationship between AQI and the incidence of rosacea.
Probiotics suppress LL37 generated rosacea-like skin inflammation by modulating the TLR2/MyD88/NF-κB signaling pathway.
Qi X, Xiao Y, Zhang X, et al. Food Funct. 2024 Aug 15. Epub ahead of print. doi:10.1039/d4fo03083d
Rosacea, a chronic inflammatory dermatological condition, is characterized by facial erythema and pustules. Recent investigations have delved into the interplay between the gut microbiota and rosacea pathogenesis, unveiling promising avenues for therapeutic intervention. In this study, we screened and isolated strains Ligilactobacillus salivarius 23-006 and Lacticaseibacillus paracasei 23-008 from the feces of healthy volunteers and evaluated the intervention effects of probiotics on rosacea by constructing an LL37 induced rosacea-like mouse model. Our results showed that both L. salivarius 23-006 and L. paracasei 23-008 were probiotic strains with favourable properties. In specific, we observed that both L. salivarius 23-006 and L. paracasei 23-008 alleviated skin lesions, reduced skin inflammatory infiltrates, and decreased the expression of inflammatory factors in mice, with the combination of L. salivarius 23-006 and L. paracasei 23-008 having the most significant effect. Moreover, the combination of strains reduced the expression of cathelicidin LL37 and rosacea-associated factors by inhibiting the TLR2/MyD88/NF-κB pathway. The 16S rRNA analysis showed that the combination enhanced the intestinal barrier, restored intestinal microbiota homeostasis, and up-regulated the abundance of Lactobacillus while down-regulating the abundance of Coprococcus and Oscillospira. We also explored the effects of postbiotics of L. salivarius 23-006 and L. paracasei 23-008 on rosacea. While postbiotics could also ameliorate the rosacea-like phenotype in mice via the TLR2/MyD88/NF-κB pathway, the effects were not as pronounced as those observed with probiotic treatment. However, the postbiotics still enhanced the intestinal barrier, up-regulated the Lactobacillus abundance, and modulated the intestinal microbiota. In conclusion, our study revealed that L. salivarius 23-006 and L. paracasei 23-008 improved rosacea by regulating the TLR2/MyD88/NF-κB pathway and intestinal microbiota, providing a theoretical basis for the treatment of rosacea.
A comparative exploration of immunohistochemical markers in patients with papulopustular rosacea undergoing treatment with oral isotretinoin versus doxycycline.
Picosse F, Rocha MA, Costa CS, et al. Int J Dermatol. 2024 Aug 4. Epub ahead of print. doi:10.1111/ijd.17420
Background: Rosacea is a chronic inflammatory disease, and doxycycline is a widely recommended treatment for it due to its anti-inflammatory action. Oral isotretinoin reduces sebaceous gland activity and modulates toll-like receptors, reducing inflammation. Our aim was to investigate the effect of these two drugs on the expression of cutaneous immunohistochemical biomarkers related to etiopathogenic factors involved in rosacea.
Methods: We conducted a randomized, comparative, and evaluator-blinded trial, including 40 participants with moderate and severe papulopustular and ocular rosacea. Participants were treated with doxycycline (DOXY) 100 mg or isotretinoin (ISO) 0.3 mg/kg daily. Immunohistochemistry at baseline and after 4 months was used to demonstrate the expression of the biomarker on the affected skin.
Results: The following changes were detected: a reduction in the vessel count after using VEGF with DOXY (P = 0.010); a decrease in VEGF intensity with ISO (P < 0.001) and DOXY (P = 0.020); a reduction of nitric oxide synthase enzyme with both drugs in the inflammatory infiltrate (ISO P < 0.001; DOXY P = 0.003); however, only with ISO was there a significant (P = 0.030) decrease at the level of the sebaceous glands, indicating a reduction of nitric oxide synthesis; a reduction of TRPV-1 expression at the level of the sebaceous glands was observed only with DOXY (P = 0.041); a decrease of cathelicidin LL37 expression, a key antimicrobial peptide in the etiopathogenesis of rosacea, was noted with both drugs, although at the level of sebaceous glands, only with DOXY (P = 0.007).
Conclusions: Oral isotretinoin and doxycycline have modified the expression of cutaneous biomarkers related to rosacea etiopathogenesis, demonstrating their role in controlling inflammatory and vascular processes.
Case Reports
Successful rhinophyma treatment utilizing the Versajet II hydrosurgery system: A case teport and systematic review of the literature.
Fuenmayor P, Gottenger R, Pujadas Z, Varma B. Cureus. 2024 Jul 5;16(7):e63921. doi:10.7759/cureus.63921
Rhinophyma, characterized by hypertrophy of sebaceous glands, often necessitates surgical intervention. This is the second case report of the off-label use of the Versajet II Hydrosurgery System (VJHS) (Smith & Nephew, London, UK) in the United States for the treatment of rhinophyma and the first systematic review of the literature, emphasizing its efficacy and safety for this indication. A surgical debulking and resurfacing was performed on a patient with rhinophyma. The patient underwent general anesthesia along with bilateral infraorbital blocks and local infiltration of lidocaine 1% with epinephrine. The VJHS was utilized for progressive debulking followed by debridement using sharp instruments until the desired nasal form and contour were achieved. Hemostasis was obtained through monopolar electrocautery and topical hemostatic agents. The patient exhibited excellent nasal shape and healing following VJHS debulking and without perioperative complications, suggesting both the effectiveness and safety of the VJHS in rhinophyma treatment. A literature review was conducted using the PubMed Central database. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, employing inclusion and exclusion criteria, were utilized to narrow down results to include original studies discussing rhinophyma surgical debridement with the VJHS. Six articles were included in the review for results analysis. This case report aligns with findings from international literature, emphasizing the versatility of the VJHS in rhinophyma treatment. Notably, this report marks the second documented off-label use of the VJHS in the United States for rhinophyma. The success of this case reinforces the potential of the VJHS in treating rhinophyma. This innovative approach yielded promising outcomes in several international reports. Further research is warranted to establish a standardized protocol to validate the long-term benefits of this technology applied to rhinophyma patients.
Symptomatic bradycardia associated with topical brimonidine gel (Mirvaso) administration: a case report.
Jesudason DI, Appalanaidu N, Khan A. Eur Heart J Case Rep. 2024 Jul 10;8(7):ytae329. doi:10.1093/ehjcr/ytae329
Background: Bradycardia can have a number of different aetiologies, including as a side effect of medications. Brimonidine is a rare, but recognized, cause of bradycardia. Brimonidine is indicated in the treatment of facial erythema in rosacea when given as topical brimonidine gel (Mirvaso). It may also be administered as eye drops for raised intraocular pressure in open-angle glaucoma and ocular hypertension. Brimonidine is an alpha-2 agonist, which if systemically absorbed can present with bradycardia, hypotension, and dizziness. The authors are unaware of any other case reports regarding topical administration of Mirvaso in an adult and symptomatic bradycardia.
Case summary: We present the case of a 78-year-old man with a background of rosacea, benign prostatic hyperplasia, and hypertension who had two separate admissions with symptomatic bradycardia. Electrocardiograms showed sinus bradycardia with AV block first degree, with rate recorded as low as 31 b.p.m. during a syncopal episode. These episodes of symptomatic bradycardia were intermittent and had a temporal association with topical administration of Mirvaso. He had no further episodes of bradycardia on discontinuation of Mirvaso and has remained symptom free for over 6 months.
Discussion: The topical administration of Mirvaso should be avoided to broken or inflamed skin. This is owing to the increased risk of systemic absorption, which as in this case report, may present with bradycardia. This case reiterates the importance of completing a full medication history including all topical and parenteral medications in patients with arrhythmia.
News
JAK Inhibition With Upadacitinib and Abrocitinib Shows Potential in Rosacea Treatment
Dermatology Times
A recent study published in Frontiers in Immunology assessed the use of JAK1 inhibitors upadacitinib and abrocitinib for the treatment of refractory rosacea. Zhang et al presented 2 cases of patients who received upadacitinib and 4 cases of patients who received abrocitinib. Overall, the study authors deemed the 2 JAK inhibitors as potential promising treatment options for refractory rosacea but noted that prospective controlled studies are needed to further assess the long-term safety and efficacy of both therapeutics for the treatment of rosacea.
Skin Barrier: Repairing Damage to the Layers Underneath
Verywell Health
Problems with any of your skin barrier layers can lead to skin barrier damage and affect its function. Skin barrier damage can increase your risk for injury or infection from external sources, decrease moisture, and disrupt functions like temperature regulation.
Increased Risk of Rosacea Found in Former Smokers, But Connection is Hazy in Current Smokers
Managed Healthcare Executive
A new study published in the Journal of Cosmetic Dermatology found that those who used to smoke may have a higher risk of developing rosacea, but there doesn't seem to be a connection between folks who currently smoke and the skin condition.
Rosacea 101: My Favourite Make Up For Rosacea
Talonted Lex
“I get asked about make up for rosacea a lot, so I thought I’d put a few of my top recommendations in one handy blog post.”