Rosacea and the cardiovascular system

Rosacea and the cardiometabolic syndrome are both associated with chronic inflammation and a pro‐inflammatory phenotype. Emerging clinical evidence supports the relationship between rosacea and cardiometabolic syndrome hypertension and obesity. This article reviews our current findings and understanding in the skin and cardiovascular relationship in rosacea. Rosacea appears to be associated with hypertension, dyslipidemia, and obesity. The role of smoking in rosacea is currently less clear. It remains uncertain whether treatment of these risk factors will aid improvement of rosacea. Greater understanding of rosacea and its association with the cardiovascular system and underlying risk factors could allow for a greater understanding of the body's inflammatory response as well as the formulation of new guidelines for attending clinicians. Dermatologists treating rosacea patients might need to consider enquiring and evaluate their patients' underlying cardiovascular risk factors.     

Rosacea: II. Therapy

Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtypes of rosacea include erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. These phenotypic expressions are probably caused by divergent pathogenic factors and consequently respond to different therapeutic regimens. A subtype-directed approach to therapy is discussed in part II of this review. We provide an overview of the available topical, oral, laser, and light therapies in the context of these cutaneous subtypes, review the evidence that supports their use, and outline their therapeutic approach. Suggestions for future areas of study also are provided. Learning objective At the completion of this learning activity, participants should be familiar with the subtype-directed approach to therapy for rosacea including available topical, oral, laser, and light therapies.     

Sensitive skin and rosacea: nosologic framework

Flushing due to rosacea may be mistaken for sensitive skin, which can manifest as abnormal sensations during fairly acute reactions to a variety of triggers, many of which are shared by rosacea and sensitive skin. Nevertheless, the two conditions are clearly different. Rosacea is a vascular disease, worsens gradually over time, manifests as flares triggered chiefly by systemic factors, is largely confined to the facial and/or ocular regions, and responds to specific treatments. Sensitive skin, in contrast, is an epidermal cosmetic problem that runs a variable course, with diffuse skin involvement and flares triggered mainly by contact factors. The flares respond to specific cosmetics and are usually worsened by treatments for rosacea.     

Rosacea: current thoughts on origin

Rosacea is a clinical pattern beginning and evolving in the genetically susceptible individual in response to a host of exposures. It produces a variety of clinical presentations, which vary over time and with age. Recently, many specific mediators of rosacea development have been described. A primary genetic cause for rosacea is suggested as single genes often control such mediators: enzymes, neuroendocrine transmitters, and cytokines are found in pathways to rosacea signs and symptoms. Currently, neither a specific cause nor a laboratory indicator of rosacea has been suggested. However, broadening interest in rosacea portends future increase in knowledge.     

Rosacea: The cytokine and chemokine network

Rosacea is one of the most common dermatoses of adults. Recent studies have improved our understanding of the pathophysiology of rosacea. Current concepts suggest that known clinical trigger factors of rosacea such as UV radiation, heat, cold, stress, spicy food, and microbes modulate Toll-like receptor signaling, induce reactive oxygen species, as well as enhance antimicrobial peptide and neuropeptide production. Downstream of these events cytokines and chemokines orchestrate an inflammatory response that leads to the recruitment and activation of distinct leukocyte subsets and induces the characteristic histopathological features of rosacea. Here we summarize the current knowledge of the cytokine and chemokine network in rosacea and propose pathways that may be of therapeutic interest.     

Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea

Rosacea is a frequent chronic inflammatory skin disease of unknown etiology. Because early rosacea reveals all characteristics of neurogenic inflammation, a central role of sensory nerves in its pathophysiology has been discussed. Neuroinflammatory mediators and their receptors involved in rosacea are poorly defined. Good candidates may be transient receptor potential (TRP) ion channels of vanilloid type (TRPV), which can be activated by many trigger factors of rosacea. Interestingly, TRPV2, TRPV3, and TRPV4 are expressed by both neuronal and non-neuronal cells. Here, we analyzed the expression and distribution of TRPV receptors in the various subtypes of rosacea on non-neuronal cells using immunohistochemistry, morphometry, double immunoflourescence, and quantitative real-time PCR (qRT-PCR) as compared with healthy skin and lupus erythematosus. Our results show that dermal immunolabeling of TRPV2 and TRPV3 and gene expression of TRPV1 is significantly increased in erythematotelangiectatic rosacea (ETR). Papulopustular rosacea (PPR) displayed an enhanced immunoreactivity for TRPV2, TRPV4, and also of TRPV2 gene expression. In phymatous rosacea (PhR)-affected skin, dermal immunostaining of TRPV3 and TRPV4 and gene expression of TRPV1 and TRPV3 was enhanced, whereas epidermal TRPV2 staining was decreased. Thus, dysregulation of TRPV channels also expressed by non-neuronal cells may be critically involved in the initiation and/or development of rosacea. TRP ion channels may be targets for the treatment of rosacea.     

Rosacea and its management: an overview

BACKGROUND: Rosacea is a chronic inflammatory disorder that affects 10% of the population. The prevalence of rosacea is highest among fair-skinned individuals, particularly those of Celtic and northern European descent. Since a cure for rosacea does not yet exist, management and treatment regimens are designed to suppress the inflammatory lesions, erythema, and to a lesser extent, the telangiectasia involved with rosacea. OBJECTIVES: This review outlines the treatment options that are available to patients with rosacea. METHODS: Published literature involving the treatment or management of rosacea was examined and summarized. RESULTS: Patients who find that they blush and flush frequently, or have a family history of rosacea are advised to avoid the physiological and environmental stimuli that can cause increased facial redness. Topical agents such as metronidazole, azelaic acid cream or sulfur preparations are effective in managing rosacea. Patients who have progressed to erythematotelangiectatic and papulopustular rosacea may benefit from the use of an oral antibiotic, such as tetracycline, and in severe or recalcitrant cases, isotretinoin to bring the rosacea flare-up under control. Treatment with a topical agent, such as metronidazole, may help maintain remission. Patients with ocular involvement may benefit from a long-term course of an antibiotic and the use of metronidazole gel. A surgical alternative, laser therapy, is recommended for the treatment of telangiectasias and rhinophyma. Patients with distraught feelings due to their rosacea may consider cosmetic camouflage to cover the signs of rosacea. CONCLUSIONS: With the wide variety of oral and topical agents available for the effective management of rosacea, patients no longer need to feel self-conscious because of their disorder.     

Rosacea and the gastrointestinal system

Rosacea is a common skin condition characterised by erythema, papules and pustules. Increasing evidence suggests that the gut–skin axis is implicated in the pathogenesis of rosacea. Sufficient evidence exists to support the notion that the gut microbiome plays a role in the inflammatory cutaneous response and there appear to be associations with small intestinal bacterial overgrowth and Helicobacter pylori infection. A dysbiotic microbiome and an innate immune system dysregulation contribute to the pathophysiology of rosacea, and further exploration of their roles is warranted. Greater understanding of this condition and the effect of the gut–skin axis could allow for more efficacious and timely treatment. This article reviews our current findings and understanding in the skin and gut relationship in rosacea.     

中国玫瑰痤疮诊疗指南（2021版）

【摘要】 玫瑰痤疮是一种好发于面中部的慢性炎症性皮肤病,主要表现为面中部反复潮红、红斑。近年来,对本病的诊治有了新的认识,为此,组织部分专家在《中国玫瑰痤疮诊疗专家共识（2016）》的基础上制定本指南,新版指南提出了分部位诊断标准,希望能进一步规范我国玫瑰痤疮的诊断与治疗。     

Effect of Oral Inhibitors of Ovulation in Treatment of Rosacea and Dermatitis Perioralis in Women

It has been known for many years that endocrine disorders have been found in women with rosacea. This disease is found more commonly in women who have menstrual abnormalities, or who are postmenopausal. There is, however, a paucity of adequate reports on the effect of simple hormonal therapy in the treatment of rosacea. This has prompted a systematic, longterm study of the influence of an oral ovulation inhibitor, namely Ovosiston, on this unpleasant and unsightly disorder.     

Granulomatous rosacea: unusual presentation as solitary plaque

A 45-year-old male presented with a 6 month history of an enlarging smooth, erythematous plaque over the central part of his face. Mild erythema of both eyes was present. Sarcoidosis, Hansen disease, lupus vulgaris, cutaneous leishmaniasis, pseudolymphoma, foreign body granuloma, granuloma faciale, discoid lupus erythematosus, and granulomatous rosacea were considered in the differential diagnosis. CBC, urinalysis, renal function tests, liver function tests, serum electrolytes, and blood sugar were all normal. Chest X-ray and ECG revealed no abnormality. Serology for syphilis and HIV, and mantoux test were negative. Slit-skin smear, tissue smear and culture for AFB and fungi were negative. Skin biopsy revealed multiple non-caseating epitheloid granulomas around the pilosebaceous unit suggestive of granulomatous rosacea. Granulomatous rosacea, a rare entity comprising only about 10 percent of cases of rosacea can mimic many granulomatous conditions both clinically and histologically making the diagnosis an enigma. It usually presents as yellowish brown-red discrete papules on the face; non-caseating epithelioid granulomas are seen on histology examination. We herein report the case because it presented in atypical fashion, as a solitary indurated plaque on the nose, likely representing Morbihan's disease or solid persistent facial edema of rosacea (rosacea lymphedema).     

酒渣鼻局部药物治疗进展

酒渣鼻是发生在中年人鼻部及面部的一种慢性炎症性皮肤病。可能是由于各种因素引起患部神经失调、毛细血管长期扩张所致。酒渣鼻治疗是一个长期的过程,由于系统给药会出现许多不良反应,而且,有研究表明,系统给药与外用药物治疗具有相同的疗效。因此,临床上多选用局部药物治疗。     

Rosacea: a wholistic review and update from pathogenesis to diagnosis and therapy

Rosacea is a chronic inflammatory disorder of the central face with multiple overlapping presentations. Recent advancements are reshaping our understanding of rosacea from both a pathophysiologic perspective and clinical approach to therapy, introducing novel agents that have improved patient outcomes and reduced morbidity. In this article, we aim to outline the advancements in understanding, diagnosing, and managing rosacea and to familiarize physicians with the literature, thereby allowing us to better practice safe and effective medicine.     

Rosacea: Treatment targets based on new physiopathology data

Over the past 15 years, numerous clinical, epidemiological and physiopathological articles have been published on rosacea. There is now increasing evidence that rosacea is an inflammatory disease characterised by abnormal innate immune response, major vascular changes, and increased colonisation by Demodex mites, along with a genetic predisposition and multiple external aggravating factors. It is thus possible to define treatment targets and possible treatments: 1) permanent vascular changes (medical and instrumental treatments); 2) flushing (betablockers, botulinum toxin); 3) innate immunity (antibiotics, nonspecific antioxidants and anti-inflammatory molecules); 4) a neurovascular component (analgesics, antidepressants); 5) Demodex (antiparasitic drugs); 6) microbiome; 7) skin barrier impairment (cosmetics and certain systemic drugs); 8) sebaceous glands (isotretinoin, surgery); 9) environmental factors (alcohol, coffee, UV exposure). Treatment recommendations are now available in many countries and benefit from the new phenotypic approach to rosacea, in which every sign or symptom is considered separately rather than having to deal with overlapping subtypes. Since the 2000s, many good quality clinical trials have been published in the field of rosacea and many others are still ongoing. Rosacea is a complex disease involving many different mechanisms and with numerous possible treatments, but there are still some important unmet needs with regard to optimal care.     

幽门螺杆菌和酒渣鼻关系的研究进展

酒渣鼻是发生在中年人鼻部及面部的一种慢性炎症,许多因素参与了其发病机制,一些学者认为幽门螺杆菌在酒渣鼻的发病机制中扮演了重要角色,其伴随产生的细胞毒素和细胞因子在酒渣鼻的发生和发展中起着重要作用,本文综述了幽门螺杆菌和酒渣鼻的关系以及幽门螺杆菌的检查方法和治疗。     

Rosacea – global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group

Background The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. Objectives The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. Methods The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. Results New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein‐5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein‐5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy – the triad of rosacea care – that integrates patient education including psychological and social aspects, skin care with dermo‐cosmetics as well as drug‐ and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. Conclusion The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence‐based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time.     

Topische Therapie der Rosazea

Metronidazole and azelaic acid are the only topical medications approved for rosacea. All other topical treatments for rosacea and its special forms are used off-label. Topical steroids are not indicated in rosacea, because of their side effects (induction of steroid rosacea, high risk of facial skin atrophy, and high risk of rebound after cessation of therapy). Topical as well as systemic steroids are allowed only as initial and short term therapy for acute forms of rosacea (e.g. rosacea fulminans). Papular and pustular rosacea is the major indication for topical therapy. Sebaceous gland and connective tissue hyperplasia in glandular-hypertrophic rosacea as well as erythema in erythematous rosacea do not respond well to topical measures. A new active substance, the alpha-2-adrenoreceptor agonist brimonidine, will be approved soon for the topical treatment of erythema in rosacea. All severe forms of rosacea should initially be treated with a combination of topical and systemic agents. After improvement of the clinical symptoms, topical treatment alone is usually adequate to maintain the control.     

Rosazea

Systemic isotretinoin has been known for decades as an effective and safe therapeutic option in the treatment of severe and refractory forms of rosacea. It can also be used in special treatment-resistant forms of rosacea, e.g. granulomatous rosacea, as efficacious second-line therapy. Previously, the effect of isotretinoin in rosacea has been mainly studied in small cohorts or anecdotal reports. Recently, a big randomized double-blind dose-response and comparative study revealed that an optimized dosage of 0,3 mg/kg was superior to other dosages and non-inferior to doxycycline as gold standard of systemic rosacea treatment and proved effective and safe in papulopustular and phymatous subtypes. However, the substance is still not licensed for this indication The efficacy of isotretinoin in rosacea is probably mainly related to anti-inflammatory mechanisms as well as anti-oxidative, anti-angiogenic and antifibrotic properties. The classical antiseborrheic effect of isotretinoin might play a role in special subtypes like the phymatous type or rosacea fulminans.     

New antibiotic therapies for acne and rosacea

Acne and rosacea compromise a substantial portion of the dermatology clinical practice. Over the past century, many treatment modalities have been introduced with antibiotics playing a major role. Today, both oral and topical antibiotics are used in the management of acne and rosacea, with several novel formulations and/or combination regimens recently introduced. The latest studies suggest anti-inflammatory actions to be the most likely mechanism of antibiotics in acne and rosacea, shifting the focus to subantimicrobial-dose oral antibiotics and/or topical antibiotic regimens as the preferred first-line agents. Here we will discuss the most recent oral and topical antibiotic therapies available for treatment of acne and rosacea, with special focus on efficacy data, indication, dosing, and mechanism of action.