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.

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.

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.

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.

[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.

Quality of life measurement in rosacea. Position statement of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa.

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient-Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa (ARHS) do not recommend the use of any generic instrument as a single method of Health Related (HR) QoL assessment in rosacea, except when comparing quimp (quality of life impairment) in rosacea patients with that in other non-dermatologic skin diseases and/or healthy controls. The EADV TFs on QoL and Patient-Oriented Outcomes and ARHS recommend the use of the dermatology-specific HRQoL instrument the Dermatology Life Quality Index (DLQI) and the rosacea-specific HRQoL instrument RosaQoL in rosacea patients. The DLQI minimal clinically important difference may be used as a marker of clinical efficacy of the treatment and DLQI score banding of 0 or 1 corresponding to no effect on patients' HRQoL could be an important treatment goal. This information may be added to consensuses and guidelines for rosacea.

Use of Patient-Reported Outcomes in Acne Vulgaris and Rosacea Clinical Trials From 2011 to 2021: A Systematic Review.

Importance: Acne and rosacea have substantial implications for quality of life, and it is therefore important to ensure the patient's voice is being captured in pivotal randomized clinical trials (RCTs). Although patient-reported outcome measures (PROMs) are a valuable tool to capture the patient perspective, little is known about use of PROMs in RCTs on acne and rosacea. Objective: To characterize the use of PROMs in RCTs on acne and rosacea. Evidence Review: A systematic literature search was conducted using the search terms acne vulgaris and rosacea in the following databases: MEDLINE through PubMed, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. A modified search hedge for RCTs from the McGill Library was applied. All phase 2, 3, and 4 RCTs published between December 31, 2011, through December 31, 2021, that evaluated the efficacy and safety of therapies for acne and rosacea vs any comparator were eligible for inclusion. Findings: A total of 2461 publications describing RCTs were identified, of which 206 RCTs met the inclusion criteria (163 trials [79%] on acne and 43 [21%] on rosacea). At least 1 PROM was used in 53% of trials (110) included; PROM use was more common in rosacea RCTs (67% [n = 29]) compared with acne RCTs (50% [n = 81]). At least 1 dermatology-specific (13% [n = 27]) or disease-specific (14% [n = 28]) PROM was included in the RCTs analyzed. Only 7% of trials (14) included a PROM as a primary outcome measure. There was no statistically significant increase in PROM inclusion over the study period (11 of 21 trials in 2011 vs 5 of 12 trials in 2021). Conclusions and Relevance: In this systematic review, PROMs were included in approximately one-half of acne and rosacea RCTs performed over the study period. In addition, PROMs were rarely used as a primary outcome measure, and inclusion of PROMs has not increased substantially over the past 10 years. Increasing use of PROMs in RCTs can ensure that the patient's perspective is captured during the development of new treatments for acne and rosacea.

Prospective evaluation of intense pulsed light treatment for meibomian gland dysfunction and blepharitis due to ocular rosacea

Background: Ocular rosacea is a common skin condition leading to dry eye that is difficult to manage. Objectives: To estimate the efficacy and safety of a new intense pulsed light device, Thermaeye Plus, for meibomian gland dysfunction and blepharitis due to ocular rosacea. Materials & Methods: This prospective, longitudinal study included 74 eyes of 37 consecutive patients with ocular rosacea, with mean age of 45.6±11.7 years. Four consecutive sessions were undertaken, including14 flashes with 10 J/cm² on the periocular area and facial cheeks on Day 1, 14, 28, and 49. Clinical evaluation was based on: ocular surface disease index (OSDI) and symptom score questionnaires, quality of live and facial severity degree, non-invasive tear meniscus height, non-invasive tear break up time, corneal fluorescein staining and eyelid margin and meibomian gland assessment. Adverse effects on the eye and periocular area, and systemic complications were evaluated. Results: The OSDI questionnaire showed a decrease in symptoms, achieving normal values in 91.9% of patients. The symptom score showed amelioration, with the most significant changes relating to dryness, foreign body sensation, light sensitivity, and pain. Longitudinal analysis showed the most significant improvement between baseline at Day 1 and 49. All eyelid signs improved, most significantly for telangiectasia/vascularity and blepharitis, leading to a 78% clearance of facial rosacea and 81.1% reduction of flushing. In total, 100% of the patients reported an improvement in their quality of life after treatment and 94.6% a very significant improvement (p<0.001). Conclusion: These results demonstrate that Thermaeye Plus is an effective and safe treatment for ocular rosacea.

Supplement Article: The Role of Epidermal Barrier Dysfunction and Cutaneous Microbiome Dysbiosis in the Pathogenesis and Management of Acne Vulgaris and Rosacea.

BACKGROUND: Dysregulation of either the cutaneous microbiome (CM) or epidermal barrier function (EBF) is thought to play an increasingly important role in acne vulgaris (AV) and rosacea pathogenesis. OBJECTIVE: To review the literature regarding epidermal barrier dysfunction (EBD) and cutaneous dysbiosis in AV and rosacea and provide clinical pearls for dermatologists. METHODS: A Medline literature search was performed for relevant literature regarding EBD and dysbiosis and either AV or rosacea. An expert consensus panel was then convened to discuss article merits and distill findings into clinical pearls. RESULTS: Final review included 138 articles. Puberty may alter natural stratum corneum lipid ratios, instigating and/or exacerbating EBD in AV. Patients with severe AV have an abundance of virulent Cutibacterium acnes phylotype IA1. EBD may manifest as classic signs of rosacea and improve with treatment. While several microbial populations are dysregulated in rosacea, the effect from any singular species is unclear. Current AV and rosacea treatment regimens may mitigate inflammation but may also indiscriminately damage CM and EBF. Physiologic moisturizers and cleansers that harness pre-/pro-/postbiotics may have a role in restoring CM, EBF, and potentially improving dermatosis severity. LIMITATIONS: Limited prospective clinical trial data especially regarding over-the-counter (OTC)/non-prescription skincare products. CONCLUSION: Appropriately developed prescription and OTC preparations may selectively influence the microbiome and potentially maintain/restore EBF. By understanding this relationship, dermatologists will be better able to educate patients on the importance of appropriate skin care.J Drugs Dermatol. 2022;21:9(Suppl 2):s5-14.

Intense pulsed light treatment for inflammatory skin diseases: a review.

Although intense pulsed light (IPL) has been commonly used in the field of medical cosmetics in recent years, the exact outcomes of IPL in the treatment of inflammatory skin diseases remain unclear. To assess the clinical evidence for the use of IPL in the treatment of various inflammatory skin diseases and propose evidence-based recommendations, we searched for relevant publications in the PubMed and Web of Science databases and provided updated information. The inflammatory skin diseases treated with IPL consisted of acne vulgaris, rosacea, psoriasis, hidradenitis suppurativa (HS), atopic dermatitis (AD), Riehl's melanosis, lupus erythematosus, cutaneous sarcoidosis, pilonidal cysts, and pigmented actinic lichen planus (PALP). The efficacy of IPL treatment for these inflammatory skin diseases was described and evaluated. Forty-two studies were included to provide this assessment. The evidence suggests that IPL can effectively and safely improve acne vulgaris and rosacea (recommendation grade B). For other described inflammatory skin diseases, IPL can be used as a tentative or supplementary treatment (recommendation grade C and D). The main complications include transitory erythema, edema, and pain, with the possibility of hyperpigmentation, blisters, and a burning sensation in some individuals.

Integrative skincare trial of intense pulsed light followed by the phyto-corrective mask, phyto-corrective gel, and resveratrol BE for decreasing post-procedure downtime and improving procedure outcomes in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory skin condition of varying severity that can significantly impact patient quality of life. Intense pulsed light (IPL) is an established treatment for rosacea-associated telangiectasia, inflammation, and erythema. This study assessed whether application of a phyto-corrective mask, gel, and resveratrol antioxidant serum after IPL treatment can improve outcomes and reduce procedure-related adverse effects. METHODS: In a prospective, open-label, split-face, 3-month study, 10 subjects with moderate-to-severe facial rosacea underwent IPL treatment on both sides of the face. The following were applied to the right side of the face only: phyto-corrective mask once weekly starting immediately after IPL; phyto-corrective gel twice daily; and resveratrol antioxidant treatment at night. Both sides of the face were treated with sunscreen. Subjects were assessed on Day 1, 1 and 3 months after IPL by three, independent evaluators using the 5-point Global Aesthetic Improvement Scale (GAIS). All subjects rated skin redness, hydration, and overall improvement on Day 1 and completed a patient satisfaction questionnaire at the 1- and 3-month visits. RESULTS: Ten women were enrolled, aged 44-72 years old, with moderate (n = 6) to severe (n = 4) rosacea. IPL was effective at reducing symptoms with rosacea classified as absent in five women and mild in five at the final 3-month visit. GAIS scores also revealed improvements on both sides of the face, but the skincare treated side showed continuous improvement over 3 months with all patients remaining at least "Improved", whereas there appeared to be a waning effect after 1 month with IPL alone. On Day 1 after IPL, all women reported less redness, improved hydration, and improved skin appearance on the right side of the face. Patient satisfaction was consistently rated higher on the right side of the face. CONCLUSION: Application of a phyto-corrective mask, gel, and resveratrol antioxidant serum may complement IPL treatment for rosacea by enhancing treatment outcomes and reducing procedure-related symptoms.