Update on rosacea classification and its controversies.

Rosacea is an inflammatory skin condition that, despite its prevalence, remains imperfectly understood. Without "gold standard" laboratory markers, the diagnosis depends greatly on clinical judgment and the nomenclature used. Throughout the years, the classification schemas for rosacea have changed as clinicians and researchers study the condition. Herein, we highlight the fundamental differences between the proposed classification systems for rosacea, emphasize the areas for improvement, and discuss the implications on clinical decision-making and patient care.

Spanish Consensus Document on the Treatment Algorithm for Rosacea. / Documento de consenso español para el algoritmo de tratamiento de la rosácea.

Recent scientific evidence and the incorporation of new drugs into the therapeutic arsenal against rosacea have made it necessary to review and update treatment criteria and strategies. To this end, a panel of 15 dermatologists, all experts in rosacea, was formed to share experiences and discuss treatment options, response criteria, and changes to treatment. Based on a critical review of the literature and a discussion of the routine practices of Spanish dermatologists, the panel proposed and debated different options, with consideration of the experience of professionals and the preferences of patients or equality criteria. Following validation of the proposals, the final recommendations were formulated and, together with the evidence from the main international guidelines and studies, used to produce this consensus document. The goal of this consensus document is to provide dermatologists with practical recommendations for the management of rosacea.

Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments.

BACKGROUND: Rosacea is a common chronic facial dermatosis. Classification of rosacea has evolved from subtyping to phenotyping. OBJECTIVES: To update our systematic review on interventions for rosacea. METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index and ongoing trials registers (March 2018) for randomized controlled trials. Study selection, data extraction, risk-of-bias assessment and analyses were carried out independently by two authors. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess certainty of evidence. RESULTS: We included 152 studies (46 were new), comprising 20 944 participants. Topical interventions included brimonidine, oxymetazoline, metronidazole, azelaic acid, ivermectin and other topical treatments. Systemic interventions included oral antibiotics, combinations with topical treatments or other systemic treatments. Several studies evaluated laser or light-based treatment. We present the most current evidence for rosacea management based on a phenotype-led approach. CONCLUSIONS: For reducing temporarily persistent erythema there was high-certainty evidence for topical brimonidine and moderate certainty for topical oxymetazoline; for erythema and mainly telangiectasia there was low-to-moderate-certainty evidence for laser and intense pulsed light therapy. For reducing papules/pustules there was high-certainty evidence for topical azelaic acid and topical ivermectin; moderate-to-high-certainty evidence for doxycycline 40 mg modified release (MR) and isotretinoin; and moderate-certainty evidence for topical metronidazole, and topical minocycline and oral minocycline being equally effective as doxycycline 40 mg MR. There was low-certainty evidence for tetracycline and low-dose minocycline. For ocular rosacea, there was moderate-certainty evidence that oral omega-3 fatty acids were effective and low-certainty evidence for ciclosporin ophthalmic emulsion and doxycycline.

Revisiting Rosacea Criteria: Where Have We Been, Where Are We Going, and How Will We Get There?

Rosacea is one of the most common and misunderstood dermatologic conditions. Currently, rosacea criteria are based on expert opinion; the definition of rosacea is primarily a reflection of opinion that is prone to bias. It has been more than a decade since the initial criteria were created by the National Rosacea Society. Revisiting the criteria and incorporating evidence-based techniques used by rheumatology and psychiatry can improve the validity and reliability of rosacea criteria. Literature from other specialties is reviewed and a method proposed for developing valid criteria. Examples are provided to motivate and highlight the importance of implementing such techniques.

Papulopustular rosacea and rosacea-like demodicosis: two phenotypes of the same disease?

BACKGROUND: Papulopustular rosacea and rosacea-like demodicosis have numerous similarities, but they are generally considered as two distinct entities, mainly because the causal role of the Demodex mite in the development of rosacea is not yet widely accepted. Several clinical characteristics are traditionally considered to differentiate the two conditions; for example, papulopustular rosacea is typically characterized by central facial papulopustules and persistent erythema, whereas small superficial papulopustules and follicular scales rather suggest rosacea-like demodicosis. However, none of these characteristics is exclusive to either entity. OBJECTIVE: To explore differences in Demodex densities according to clinical characteristics traditionally associated with these two conditions. METHODS: Retrospective, observational, case-control study of 242 patients with central face papulopustules. Demodex densities were measured on two consecutive standardized skin surface biopsies. RESULTS: In the whole cohort, Demodex densities were greater in patients with persistent erythema than in those without. In 132 patients without recent treatment or other facial dermatoses, 120 (91%) had persistent erythema, 119 (90%) small superficial papulopustules and 124 (94%) follicular scales; 116 (88%) simultaneously had clinical characteristics traditionally associated with both papulopustular rosacea and rosacea-like demodicosis. Higher Demodex densities were linked to the presence of follicular scales, but not to papulopustules size, nor to the presence/absence of persistent erythema. CONCLUSION: Our observations highlight the difficulty differentiating between these entities and suggest that rosacea-like demodicosis and papulopustular rosacea should no longer be considered as two separate entities, but rather as two phenotypes of the same disease.

Recent advances in understanding and managing rosacea.

Rosacea is a common chronic inflammatory skin disease of the central facial skin and is of unknown origin. Currently, two classifications of rosacea exist that are based on either "preformed" clinical subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) or patient-tailored analysis of the presented rosacea phenotype. Rosacea etiology and pathophysiology are poorly understood. However, recent findings indicate that genetic and environmental components can trigger rosacea initiation and aggravation by dysregulation of the innate and adaptive immune system. Trigger factors also lead to the release of various mediators such as keratinocytes (for example, cathelicidin, vascular endothelial growth factor, and endothelin-1), endothelial cells (nitric oxide), mast cells (cathelicidin and matrix metalloproteinases), macrophages (interferon-gamma, tumor necrosis factor, matrix metalloproteinases, and interleukin-26), and T helper type 1 (T H1) and T H17 cells. Additionally, trigger factors can directly communicate to the cutaneous nervous system and, by neurovascular and neuro-immune active neuropeptides, lead to the manifestation of rosacea lesions. Here, we aim to summarize the recent advances that preceded the new rosacea classification and address a symptom-based approach in the management of patients with rosacea.

Standard classification and pathophysiology of rosacea: The 2017 update by the National Rosacea Society Expert Committee.

In 2002, the National Rosacea Society assembled an expert committee to develop the first standard classification of rosacea. This original classification was intended to be updated as scientific knowledge and clinical experience increased. Over the last 15 years, significant new insights into rosacea's pathogenesis and pathophysiology have emerged, and the disorder is now widely addressed in clinical practice. Growing knowledge of rosacea's pathophysiology has established that a consistent multivariate disease process underlies the various clinical manifestations of this disorder, and the clinical significance of each of these elements is increasing as more is understood. This review proposes an updated standard classification of rosacea that is based on phenotypes linked to our increased understanding of disease pathophysiology. This updated classification is intended to provide clearer parameters to conduct investigations, guide diagnosis, and improve treatment.

Pharmacologic treatments for rosacea.

Rosacea represents a common and chronic inflammatory skin disorder. Clinical features include transient and permanent erythema, inflammatory papules and pustules, phymatous changes, and ocular signs and symptoms. Rosacea is generally classified into four subtypes and one variant. Subtype 1, erythematotelangiectatic rosacea, includes clinical features of flushing and persistent central facial erythema with or without telangiectasia. Subtype 2, papulopustular rosacea, is characterized by persistent central facial erythema with transient papules or pustules or both on the central face. Subtype 3, phymatous rosacea, includes thickening of the skin with irregular surface nodularities and enlargement. Subtype 4, ocular rosacea, includes inflammation of different parts of the eye and eyelid. A variant, granulomatous rosacea, is noninflammatory and is characterized by hard, brown, yellow, or red cutaneous papules or nodules of uniform size. Patients may present with more than one subtype, and each individual characteristic may fluctuate. There is debate whether rosacea progresses from one subtype over time or subtypes represent discreet entities. Defining clinical presentation and improved understanding of pathophysiology has resulted in identification of novel treatment approaches. This contribution outlines a rationale for treatment, highlights an evidence-based approach with approved treatments, and considers novel developments and off-license therapy available.

Epidemiology of rosacea in Colombia.

BACKGROUND: Prevalence of rosacea has been estimated around the world in the range of 0-22%. In Colombia, the prevalence of rosacea remains unknown. The aim of this study was to determine the prevalence of rosacea and the frequencies of its subtypes in Colombia. METHODS: This cross-sectional, multicenter study was conducted in six outpatient dermatology clinics across Colombia. A total of 33 dermatologists conducted a comprehensive medical history and physical examination for all rosacea patients seen at their offices over the course of 2 months. All patients who accepted to participate were encouraged to answer a survey about the history of their illness. RESULTS: Of 10,204 outpatients evaluated for rosacea between July and August 2014, 291 rosacea patients were included in this study. The prevalence of rosacea subtypes in this cohort was: 45.3% erythematotelangiectatic (ETR) (n = 132), 48.7% papulopustular (PPR) (n = 142), 4.8% phymatous (n = 14), and 1% ocular (n = 3). CONCLUSIONS: Overall, the prevalence in Colombia was 2.85%. Our data represent an important first step to understanding the current state of rosacea in Colombia. The prevalence of rosacea in Colombia is the highest in Latin America among a few reports published, which might be explained by geographic features. However, contrary to our expectations, the prevalence is lower than that in some European countries. We postulate that this finding may be due to methodological differences.

Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and secondary features and managed by subtype. However, individual features (phenotypes) can span multiple subtypes, which has implications for clinical practice and research. Adopting a phenotype-led approach may facilitate patient-centred management. OBJECTIVES: To advance clinical practice by obtaining international consensus to establish a phenotype-led rosacea diagnosis and classification scheme with global representation. METHODS: Seventeen dermatologists and three ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and severity evaluation. All voting was electronic and blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based approach to rosacea diagnosis and classification. The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes. Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not considered to be individually diagnostic. The panel reached agreement on dimensions for phenotype severity measures and established the importance of assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an approach for diagnosis and classification of rosacea based on disease phenotype.

Clinical evaluation of 30 patients with localized nasal rosacea.

The clinical features of localized nasal rosacea have not been described in detail. This study was designed to analyze the subtypes and severity of localized nasal rosacea. Our present study included 30 patients with localized nasal rosacea. The erythematotelangiectatic subtype (13/30, 43.3%) was the most common type, followed by the phymatous subtype (9/30, 30%). The duration of rosacea was shorter and the severity of localized nasal rosacea was lower in the erythematotelangiectatic subtype cases compared with the patients with mixed or phymatous subtypes. Almost all of the papulopustular eruptions or phymatous lesions were associated with erythematotelangiectatic lesions. These findings suggest that the erythematotelangiectatic subtype may be considered the initial phase of localized nasal rosacea.

Histopathological Analysis of 226 Patients With Rosacea According to Rosacea Subtype and Severity.

BACKGROUND: The histopathological features of rosacea have not been described in detail. OBJECTIVE: To evaluate the histopathological features of rosacea according to clinical characteristics such as subtype and severity. METHODS: We retrospectively analyzed histopathological findings in 226 patients with rosacea, which included 52 patients with the erythematotelangiectatic rosacea (ETR) and 174 patients with the papulopustular rosacea (PPR) subtype. The frequency of each histopathological finding was compared between subtypes. Histopathological features were also compared according to the severity, through subgroup analysis within each subtype group. RESULTS: Perivascular and perifollicular lymphohistiocytic infiltration were common dermal findings in both subtype groups, but the intensity of dermal inflammatory infiltration was higher in PPR than in ETR. Follicular spongiosis and exocytosis of inflammatory cells into hair follicles were noted in both subtypes; but these findings were significantly more common in the PPR subtype. Vascular changes (telangiectasia and proliferation) and solar elastosis were common histopathological findings in both subtypes, with no difference in frequency between subtype groups. Demodex mites were identified in about 40% of patients, and the frequency of demodex mites did not differ between subtype groups. The intensity of perifollicular inflammation and the presence of follicular inflammatory reactions were dependent on the severity of rosacea in both subtype groups. CONCLUSIONS: The intensity of inflammatory reactions, especially perifollicular infiltration, was higher in PPR patients than in ETR patients. Rosacea has a spectrum of histopathological features that are related to clinical progression between rosacea subtypes.

Prognosis of 234 rosacea patients according to clinical subtype: The significance of central facial erythema in the prognosis of rosacea.

Rosacea has a wide spectrum of clinical features, which include persistent facial redness, flushing, telangiectasia, inflammatory papules/pustules, hypertrophy and/or ocular features. The prognosis of rosacea according to clinical subtype has not been evaluated. We analyzed the prognosis of rosacea in 234 patients, which included 120 patients with mixed subtype, 75 with the erythematotelangiectatic rosacea subtype and 39 with the papulopustular rosacea (PPR) subtype. The prognosis of rosacea was classified as: (i) no improvement; (ii) partial remission; and (iii) complete remission. The frequencies of complete remission, time to complete remission and 1-year complete remission rate were compared between subtypes. Follow-up periods ranged 2-72 months (median follow-up, 17.5). Aggravation of the disease was found in 50.4% of patients during follow up. Partial or complete remission was noted in 61.5% and 20.9% of patients, respectively. The median time to complete remission was 56.0 months. The prognosis of disease was more favorable for patients with the PPR subtype than for patients with other subtypes with respect to the frequency of complete remission, median time to complete remission and the 2-year complete remission rate. In conclusion, papulopustular rosacea without remarkable centrofacial erythema showed a more favorable prognosis than other subtypes. Erythematotelangiectatic lesions in rosacea patients present a challenge for the treatment of rosacea.

[Rosacea]. / La rosacea.

Rosacea is a common centro-facial dermatosis with a high socio-esthetic impact. Different subtypes are distinguished, classified into grades according to their severity. This classification is essential for therapeutic management. In general, rosacea remains difficult to treat as its pathophysiology is still not entirely understood. Future research is needed for a better understanding of this disease and the development of targeted treatments.

Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors.

Rosacea is a chronic inflammatory skin condition that affects approximately 16 million Americans. Four distinct subtypes of rosacea have been recognized, with transient and nontransient facial flushing, telangiectasia, and inflammatory papules and pustules being among the more commonly recognized features. Although the exact pathogenesis of rosacea is unknown, dysregulation of the innate immune system, overgrowth of commensal skin organisms, and aberrant neurovascular signaling may all have a role in promoting the clinical features of rosacea.

Clinical evaluation of 368 patients with nasal rosacea: subtype classification and grading of nasal rosacea.

BACKGROUND: The clinical features of nasal rosacea have not been described in detail. OBJECTIVE: To describe the clinical features of nasal rosacea. METHODS: 599 patients were classified into those with rosacea in both the nasal and extra-nasal areas (group A), localized nasal rosacea (group B) and rosacea without nasal involvement (group C). RESULTS: The mixed subtype was more common in group A (n = 337) than in group C (n = 231). The severity score was higher in group A than in group C. Erythematotelangiectatic rosacea was the most common subtype in group B (n = 31) and was more common in group B than in group A. Rosacea mainly affected the lower half of the nose in group B, but affected the entire nose in group A. CONCLUSION: Nasal involvement may be an index of severe rosacea. Localized nasal rosacea is a separate spectrum with different clinical features.