Therapeutic strategies focusing on immune dysregulation and neuroinflammation in rosacea.

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.

Rosacea: Common Questions and Answers.

Rosacea is a chronic inflammatory skin disease of the central face, affecting 5% of the population. The exact etiology is unknown. A diagnosis is made based on the updated 2017 National Rosacea Society Expert Committee guidelines, including fixed erythema, phymatous changes of skin thickening due to sebaceous gland hyperplasia and fibrosis, papules, pustules, telangiectasia, and flushing. Delays in an accurate diagnosis and treatment may occur in skin of color due to difficulty visualizing erythema and telangiectasia. The daily use of sunscreen, moisturizers, and mild skin cleansers and avoidance of triggers are essential aspects of maintenance treatment. Effective topical treatment options include alpha-adrenergic receptor agonists for flushing and ivermectin, metronidazole, and azelaic acid for papules and pustules. Systemic treatments include nonselective beta blockers for flushing, low-dose doxycycline, and isotretinoin for papules and pustules. Rosacea can significantly affect a patient's emotional health and quality of life. A referral for care is recommended for fixed phymatous changes and ocular rosacea. (Am Fam Physician. 2024;109(6):533-542.

Challenges and real-world solutions for adoption of holistic skincare routine (cleansing, treatment, moisturization, and photoprotection) in acne, rosacea, atopic dermatitis, and sensitive skin: An expert consensus.

BACKGROUND: While treatment is a definitive therapeutic component in the management of inflammatory skin conditions, adjunctive skin care comprising of appropriate cleansing, moisturization, and photoprotection are just as important. Cleansing, treatment, moisturization, and photoprotection (CTMP) constitute the four major components of holistic skincare routine for dermatological conditions. However, inadequate patient understanding of the condition, limited resources for physicians, and insufficient time for patient education during busy dermatological consultations are the main obstacles to establishing a holistic skincare routine in the real world. AIMS: This study aimed to identify key challenges in the implementation of a holistic skincare routine, and offer practical guidance to physicians to improve adoption in the management of acne, atopic dermatitis, rosacea, and sensitive skin syndrome. METHODS: An expert panel comprising of nine dermatologists from Australia, China, Hong Kong, Taiwan, India, Philippines, Singapore, South Korea, and Thailand convened to develop consensus statements to stimulate real-world adoption of holistic skincare routine in acne, rosacea, atopic dermatitis, and sensitive skin syndrome using the Delphi approach. RESULTS: Consensus was defined as ≥80% of panel rating statement as ≥8 or median rating of ≥8. The final statements were collated to develop consensus recommendations to encourage adoption of holistic skincare routine. CONCLUSION: Promoting patient education on the skin condition, training support staff in patient counseling, and offering physician training opportunities are the key strategies to encourage real-world adoption of CTMP as a holistic skincare routine. The consensus recommendations presented here should be considered in all dermatology patients to accomplish the ultimate goals of improved treatment outcomes and patient satisfaction.

Efficacy and safety comparison between pulsed dye laser and intense pulsed light configured with different wavelength bands in treating erythematotelangiectatic rosacea.

Previous clinical studies have shown that pulsed dye laser (PDL) and intense pulsed light (IPL) are effective for treating erythematotelangiectatic rosacea(ETR). This article aims to compare the efficacy and safety of PDL and IPL at three different wavelength bands (broad-band, single-narrow-band, and dual-narrow-band) in treating ETR. Sixty subjects with ETR were randomly categorized into four groups and received one of the following laser treatments: PDL (595 nm), IPL with Delicate Pulse Light (DPL, 500-600 nm), IPL with M22 590 (590-1200 nm), or IPL with M22 vascular filter (530-650 nm and 900-1200 nm). Four treatment sessions were administered at 4-week intervals, with one follow-up session 4 weeks after the final treatment. The efficacy of the four lasers was evaluated by comparing the clinical symptom score, total effective rate, VISIA red area absolute score, and RosaQoL score before and after treatment. The safety was evaluated by comparing adverse reactions such as pain, purpura, erythematous edema, and blister. All 60 subjects completed the study. Within-group effects showed that the clinical symptom score, VISIA red area absolute score, and RosaQoL score of all four groups were significantly reduced compared to before treatment (p < 0.001). Between-group effects showed no statistically significant difference among the four laser groups. Safety analysis showed that all four lasers were safe, but the incidence of blister was higher in the M22 vascular group. Nonpurpurogenic PDL, DPL, M22 590, and M22 vascular were equally effective in treating ETR and were well-tolerated. ClinicalTrial.gov Identifier: NCT05360251.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Rosacea treatment with 532 nm KTP versus 595 nm pulsed dye laser-A prospective, controlled study.

BACKGROUND: Pulsed-dye lasers (PDL) are one of the standard therapies for rosacea, but alternatives are needed. AIMS: To compare the efficacy and safety of the variable-sequenced, large-spot 532 nm KTP laser to the 595 nm PDL in treating rosacea. MATERIALS AND METHODS: A prospective, controlled, evaluator-blinded study. Patients were treated with either a KTP or PDL with 1-3 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled on Week 6 post-treatment. Clinical outcome was assessed by computer-assisted analysis and by patients and two blinded dermatologists. Pain intensity during treatment and adverse events were documented. RESULTS: Forty-five patients (mean age 51 years) were allocated in a 2:1 ratio to either the KTP or PDL. Erythema in both treatment arms decreased significantly (p < 0.01). Clinical evaluation revealed high improvement. Mean pain intensity was significantly lower with the KTP (2.5/10) than with the PDL (4.1/10). Both lasers showed a good safety profile. Relevant purpura was only seen in the PDL group. CONCLUSIONS: Both the variable-sequenced, large-spot KTP and the PDL demonstrated comparable efficacy in treatment of rosacea. Regarding safety, the KTP exhibited fewer post-treatment reactions. The KTP might serve as a potential alternative to PDL in the treatment of rosacea.

Rosacea: Pathogenesis and Therapeutic Correlates.

Rosacea is a chronic inflammatory condition of which there is no cure. The pathogenesis of rosacea is likely multifactorial, involving genetic and environmental contributions. Current understanding suggests that pro-inflammatory pathways involving cathelicidins and inflammasome complexes are central to rosacea pathogenesis. Common rosacea triggers modulate these pathways in a complex manner, which may contribute to the varying severity and clinical presentations of rosacea. Established and emerging rosacea treatments may owe their efficacy to their ability to target different players in these pro-inflammatory pathways. Improving our molecular understanding of rosacea will guide the development of new therapies and the use of combination therapies.

Patients' testimonies, feelings, complaints and emotional experiences with dermatoses on open social media: The French infodemiologic patient's free speech study.

BACKGROUND: Dermatoses represent a significant burden. Patients and their caregivers can turn to social media and digital communities to exchange with each other. These public exchanges constitute real-life data that can be analysed to better understand the patients' feelings and expectations, and the daily difficulties encountered. OBJECTIVE: An infodemiologic study of public testimonies of patients and caregivers related to five dermatoses: eczema, rosacea, vitiligo, acne and psoriasis, over a 3-year time frame (September 2018 to September 2021) in France. To identify main topics of discussion, encountered difficulties and unmet medical needs. METHODS: Data extraction was performed based on a list of pertinent keywords. Web-users' profiles were determined by a specifically trained machine learning algorithm. Encountered difficulties were identified by manual annotation based on a standardized search grid. Co-occurrence analysis of difficulties allowed contextualization of challenges and unmet needs for each dermatosis. RESULTS: A total of 20,282 messages coming from 16,800 web users was extracted. The main topics of discussion were 'Impact on self- image and self-confidence' (23.6%), 'Generic discussion about therapeutics' (23.3%) and 'Burden of others' gaze' (12.8%). The top three mentioned difficulties for the five targeted dermatoses were similar and focused on 'Fear of/and management of symptoms', 'Impact on/and mood management' and 'Damaged self-image'. CONCLUSION: This infodemiologic study highlighted the real-life management of five skin diseases by patients and their caregivers, who turned to social networks to openly express their suffering and seek solutions. The joined analysis of the five diseases enabled a common comprehension of what it is to live with a skin disease, from a patient-centric point of view. The specific analysis of each patient group objectified specific challenges, and main unmet medical needs.

Rosacea treatment with mussel adhesive protein delivered via microneedling: In vivo and clinical studies.

BACKGROUND: Rosacea is a prevalent chronic dermatological condition marked by facial inflammation and erythema, significantly compromising the quality of life for affected individuals. Current treatment methods for rosacea are not considered ideal because of the complex etiology of the disease. Mussel adhesive protein (MAP) is a glycoprotein derived from the foot gland of mussels. The protein exhibits anti-inflammatory properties, relieves skin itching, and promotes wound healing. AIMS: We aimed to explore the feasibility of using MAP administered via microneedle delivery for treating rosacea and the potential molecular mechanism involved. MATERIALS AND METHODS: The therapeutic effect and mechanism of MAP microneedle delivery in an LL-37-induced rosacea-like mouse model were observed using morphological and histological methods. Twenty-seven patients with erythematotelangiectatic rosacea (ETR) underwent treatment once every 1 month, with three treatments constituting one treatment course. The therapeutic effect was evaluated by comparing the clinical images taken at baseline, after the first treatment course, and after the second treatment course. The red value, CEA, and GFSS score were also calculated. RESULTS: In response to the microneedle delivery of MAP, innate immunity, inflammatory infiltration, and abnormal neurovascular regulation improved significantly in rosacea-like mice. In the clinical experiments, the microneedle delivery of MAP significantly improved the symptoms of erythema, flushing, and telangiectasia in patients with ETR, and no obvious adverse reactions were observed. CONCLUSIONS: MAP delivered by microneedling is effective and safe for treating ETR.

Diagnosis and Management of Common Inflammatory Skin Diseases in Older Adults.

Inflammatory skin conditions affect people of all ages, genders, and races. These common conditions are frequent causes of visits to the dermatologist. The geriatric population is often afflicted by these conditions because many are chronic and relapsing diseases. These inflammatory conditions include but are not limited to psoriasis, atopic dermatitis, contact dermatitis, seborrheic dermatitis, rosacea, and Grover disease. Chronic inflammatory skin conditions place a large burden on the health care system in the United States and have many associated comorbidities. This article discusses these inflammatory dermatoses that affect the geriatric population and common therapeutic options.

Rosacea: Clinical Aspects and Treatments.

GENERAL PURPOSE: To review the clinical presentation and treatment of rosacea. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Distinguish the clinical manifestations of rosacea subtypes.2. Identify pharmacologic and nonpharmacologic treatment options for patients who have rosacea.

Rosacea is a chronic inflammatory disease characterized by a diverse set of nonspecific clinical signs including erythema, flushing, papules and pustules, skin thickening (especially enlarged nose) and thread-like vessels in the central facial region, and potential ocular involvement. This review focuses on the epidemiology, clinical presentation, and treatment of rosacea. Other related topics discussed include the psychosocial impact and differential diagnoses.

Narrow-Band Intense Pulsed Light as Treatment for Erythematotelangiectatic Rosacea: A Retrospective Study.

BACKGROUND: Erythematotelangiectatic rosacea can be successfully treated using various laser and light-based devices. However, the use of narrow-band intense pulsed light for the treatment of erythematotelangiectatic rosacea has not been investigated in detail. This retrospective study aimed to analyze the clinical efficacy of narrow-band intense pulsed light (500-600 nm) for the treatment of erythematotelangiectatic rosacea among Chinese individuals.  Methods: Patients with erythematotelangiectatic rosacea who had completed 3 sessions of treatment with narrow-band intense pulsed light and follow-up from July 2016 to December 2018 were retrospectively evaluated. Clinical improvement was assessed by 2 blinded dermatologists based on photographs obtained at each follow-up visit using the clinician erythema assessment scale and 5-grade scale. RESULTS: Forty-five patients with erythematotelangiectatic rosacea treated with narrow-band intense pulsed light were included in this study. The effectiveness and excellent rates after 3 treatment sessions were 68.9% and 35.6%, respectively. An average of 2 treatment sessions was required among patients who achieved good or excellent clearance of erythema and telangiectasia. Except for transient erythema and edema, no severe adverse effects were observed. CONCLUSIONS: Narrow-band intense pulsed light is a safe and effective treatment for erythematotelangiectatic rosacea. Even with a small number of treatment sessions, narrow-band intense pulsed light can deliver a significant therapeutic effect, which may be applicable in clinical practice. J Drugs Dermatol. 2023;22(11):1095-1098     doi:10.36849/JDD.4920.

[Comorbidity of rosacea and various pathological conditions among the population of the countries of the world, accounting for treatment and preventive measures].

Currently, there is an urgent need for global research to develop a modern comprehensive study of rosacea, including its pathogenesis, risk factors, association of rosacea subtypes with concomitant diseases. The most relevant research studies the role of immunity and microorganisms in the pathogenesis of rosacea. To elucidate the features of the comorbidity of rosacea and somatic diseases, studies in various populations with detailed clinical data and a longer follow-up period are important. At the same time, it is important to understand the relationship between the severity and severity of various clinical symptoms of rosacea, the mechanisms that regulate the progression of the process, the combination of rosacea subtypes and the course of the disease in association with other forms of pathological disorders.

The role of macrophages in rosacea: implications for targeted therapies.

Introduction: Rosacea, a widespread chronic skin condition, may be influenced by macrophages, key immune cells in the skin, although their exact role is not yet fully understood. This review delves into the function of macrophages, their potential contribution to rosacea pathogenesis, current treatments, and promising macrophage-targeted therapies. It concludes by identifying knowledge gaps and potential areas for future rosacea research. Method: Leveraging systematic and narrative literature review techniques, we conducted a comprehensive search of databases such as PubMed, Embase, and Web of Science. Utilizing keywords like "rosacea" and "macrophages", we targeted English articles from the last 5 years (2018-2023). We manually checked reference lists of relevant articles for additional studies. We included only articles emphasizing macrophages' role in rosacea and/or the development of related therapies and published within the specified timeframe. Results: The systematic search of electronic databases yielded a total of 4,263 articles. After applying the inclusion and exclusion criteria, 156 articles were selected for inclusion in this review. These articles included original research studies, review articles, and clinical trials that focused on the role of macrophages in rosacea and/or the development of macrophage-targeted therapies for the disease. The selected articles provided a comprehensive and up-to-date overview of the current state of research on macrophages in rosacea, including their function in the skin, the potential mechanisms through which they may contribute to rosacea pathogenesis, and the current treatments and therapies available for the disease. Additionally, the articles identified gaps in knowledge regarding the role of macrophages in rosacea and suggested potential areas for future research. Conclusion: This literature review emphasizes the important role that macrophages, vital immune cells in the skin, may play in the pathogenesis of rosacea, a common chronic inflammatory skin disorder. The selected studies suggest potential mechanisms by which these cells might contribute to rosacea progression, although these mechanisms are not yet fully understood. The studies also spotlight current rosacea treatments and illuminate the promising potential of new macrophage-focused therapies. Despite these insights, significant gaps persist in our understanding of the precise role of macrophages in rosacea. Future research in this area could provide further insights into the pathogenesis of rosacea and contribute to the development of more effective, targeted therapeutic strategies.

Rosacea: The eyes have it.

Rosacea is a chronic inflammatory dermatosis typically affecting the facial skin but also the eyes. With its chronic course with fluctuating episodes of flashing, redness, papulopustules, and nodules it poses a severe psychologic burden to the affected individuals. In addition to the facial changes, more than half of the patients have ocular involvement ranging from blepharitis and conjunctival hyperemia to more severe ophthalmic damage, and even blindness. Clinically, the ocular involvement in rosacea includes meibomian gland dysfunction with relapsing hordeola and chalazia, diffuse hyperemic conjunctivitis, photophobia, episcleritis, or kerato-conjunctivitis, and in rare cases, corneal ulcers. These are mainly observed in adult patients but can also occur in children. Depending on the degree of cutaneous or ocular findings, patients with rosacea may present first to the dermatologist or to the ophthalmologist. Both specialists should be aware of the potential oculocutaneous involvement. Any ocular complaints expressed by the patient in the setting of a dermatologist's office should be referred promptly for an ophthalmologic examination. Conversely, signs suggestive of rosacea in the eye should lead the ophthalmologist to consider underlying skin disease. A timely interdisciplinary collaboration is paramount for the earlier diagnosis and treatment, thus preventing permanent eye impairment in this chronic dermatosis.

A new 532 nm, variable-pulse-structure, dual-wavelength, KTP laser incorporating cryogen spray cooling, effectively treats rosacea.

BACKGROUND: A new dual-wavelength, high-energy, solid-state laser incorporating both 532 and 1064 nm wavelengths was developed with cryogen spray cooling and the unique ability to deliver three types of pulse structures including single pulses of a specific pulse-duration or pulses composed of a train of subpulses in the millisecond or microsecond domain with an intervening delay over the selected pulse-duration. We investigate the efficacy of this laser using all three pulse structures and the 532 nm wavelength for treating rosacea. METHODS: Twenty-one subjects were enrolled in this IRB-approved study. A total of up to three treatments were administered at monthly intervals. Each treatment consisted of a first pass tracing linear vessels with a 40 ms pulse-duration immediately followed by a second pass using a 5 ms pulse, using all three available pulse structures. Assessment of cross-polarized digital images by blinded physician observers compared baseline and 3-month follow-up images. RESULTS: Blinded observers correctly identified the posttreatment images 89% of the time, in 17 of 19 subjects completing the study, with an average overall improvement rating of 39% after only three treatments. Side effects were limited to short-term erythema and edema. CONCLUSION: This study demonstrates that this new, variable-pulse-structure, dual wavelength, solid state, KTP laser with dynamic cooling is a safe and effective for treating rosacea.

Idiopathic facial aseptic granuloma in children: Management and long-term follow-up.

AIMS: The primary objective was to study long-term outcomes in children with idiopathic facial aseptic granuloma (IFAG). The secondary objectives were to describe the clinical polymorphism of this entity, the different therapeutic options, and the occurrence of rosacea in this population. METHODS: We selected patients with a clinical diagnosis of IFAG seen in two different hospitals in Normandy between March 2016 and February 2021, and we collected clinical and therapeutic data from computerized medical records. A remote consultation based on recent photographs was performed to collect new data, and the children's parents were asked to complete a questionnaire between February and August 2021. RESULTS: Ten children were included in this study. Nine patients presented with a single red to purplish nodule. One patient presented multiple papulopustular plaques. IFAG healed spontaneously without major sequelae, and this outcome was not influenced by any treatments. During follow-up, two patients developed childhood rosacea. CONCLUSION: Although some clinical heterogeneity exists, early diagnosis and follow-up of IFAG is necessary to avoid unnecessary topical or systemic antibiotic treatments that do not shorten the disease course. IFAG appears to be a possible mode of entry for infantile rosacea.

Ocular rosacea: an under-recognized entity.

While rosacea is a common dermatologic condition, ocular rosacea is sometimes evident either with cutaneous rosacea or occasionally by itself. Manifesting with such varied symptoms as dry eye, Meibomian gland dysfunction, and corneal erosion, ocular rosacea can be confused with a multitude of other diseases. While ocular rosacea is commonly mild and rarely severe, physicians should still expand their examination to include ocular manifestations of rosacea. In addition, we propose diagnostic criteria for ocular rosacea, stressing the importance of early recognition and treatment.