Exploring New Dimensions in Longitudinal Rosacea Management

Abstract

Rosacea is a common, chronic, inflammatory disease of the skin, which predominantly (but not exclusively) affects the centrofacial region. Clinical features may include transient or persistent facial erythema, recurrent flushing, telangiectasia, papules, pustules, phymatous changes, and ocular disturbances. These can lead to significant physical and psychological burden and discomfort, which adversely affects a patient’s quality of life (QoL). While current guidelines provide recommendations on treatment initiation and modification, there is a lack of information for long-term management and maintenance. The Rosacea–Expert Advice on Combined and Holistic approaches (REACH) group is an international group of experienced dermatologists, brought together to address these shortcomings. This paper summarizes discussions from three REACH Global Scientific Committee (GSC) meetings, with the objective to simplify the rosacea management pathway and ensure that healthcare professionals are aware of rosacea triggers, pathogenesis, risk factors, comorbidities, chronicity, patient satisfaction, monitoring, and treatment options. The REACH GSC developed a rosacea management pathway as a backbone for this publication—to advise on each step, including pitfalls to avoid, patient discussions to conduct, tools and guidelines to employ, and clinical factors to consider. Being able to discern all the clinical features of rosacea specific to each patient is imperative, from recognizing overriding signs and symptoms to understanding potential comorbidities and assessing impact on QoL. Clear and sensitive communication regarding these elements, and what outcomes are achievable, will help to optimize therapeutic management and foster a sense of patient empowerment and disease control. For patients, being able to engage in their own long-term care of symptoms, signs, and flares is critical. Deepening the understanding of the condition as a chronic, yet eminently manageable one, will help empower patients with rosacea and their dermatologists alike. The REACH GSC project was initiated and funded by Galderma.

Key Summary Points

Current challenges in the management of rosacea, are driven by suboptimal uptake of existing guidelines and a need for a streamlined approach in long-term control that provides clarity for both dermatology and nondermatology specialist healthcare professionals.

The Rosacea–Expert Advice on Combined and Holistic approaches (REACH) group held three global scientific committee (GSC) meetings to develop a rosacea management pathway covering four key steps: self-management and entry into medical pathway, diagnosis, treatment selection, and maintenance.

Through further exploration of each step of the management pathway and of clinical studies for more uncommon or difficult-to-discern types of rosacea, the GSC identified the ability to discern all clinical features and symptoms as imperative and best achieved through clear and sensitive communication with patients.

Rosacea can be a significant burden on the quality of life of those affected; however, by helping patients to understand rosacea as a chronic but manageable condition, patients are more likely to engage in their own long-term care and feel empowered to influence the fate of their disease.

Introduction

The Rosacea–Expert Advice on Combined and Holistic approaches (REACH) project evolved in response to an easily identifiable void in rosacea, to address the challenges and current gaps in holistic and integrated approaches to long-term rosacea management, patient communication, and prolonged control of signs and symptoms of rosacea. In the opinion of the REACH Global Scientific Committee (GSC), a key driver behind the project was the suboptimal uptake of guidelines on rosacea (ROSacea COnsensus [ROSCO] [1–3], American Acne and Rosacea Society [AARS] [4], and National Rosacea Society [NRS] [5]) and the need for a streamlined approach in long-term control that provides clarity for dermatology and nondermatology specialist healthcare professionals (HCPs).

We discuss clinical presentation/phenotypes, triggers, foundational skincare, and what should be considered at the first visit. Less common or more difficult-to-discern clinical presentations are also discussed, including differential diagnosis and standards of care.

The REACH GSC has recognized that there is a need to shift patient and HCP perceptions to understand that rosacea is a chronic, but manageable, disease. Despite the chronicity of the disease, clinical trials are often time constrained to the minimum time required to establish safety and efficacy; typically, a 12–16-week duration [6]. To adequately address patient needs, including longer-term control of rosacea, there is a need for guidance for effective maintenance therapy beyond the time constraints imposed by clinical trials [6].

Through this framework, the REACH GSC aims to share its extensive experience of clinical experience, research and guidance, and provide global insight.

Methods

REACH GSC

The REACH GSC is formed of experts in the field of dermatology, who specialize in rosacea diagnosis and management. The GSC encompasses 12 experts from nine countries: three from the USA, two from Germany, and one each from Australia, Brazil, Canada, Italy, Korea, Philippines, and Poland.

Framework Development

An initial survey of the REACH GSC members was conducted to identify and prioritize key challenges in long-term rosacea management across diagnosis, treatment options, treatment maintenance, patient satisfaction, and guidelines. The survey asked the GSC members to score challenges on a scale of 1–10, where 1 was “very low importance” and 10 was “very high importance.”

Following the survey, three iterative GSC meetings were held. The first aimed to prioritize themes for a management narrative, the second to create a framework flow to align patient progress with pillars, and the third to consolidate the framework.

Targeted Literature Search and Selection

To support and validate the framework developed from the GSC meetings, targeted literature searches were conducted in PubMed between 1 January 2014 and 30 April 2025. Key words searched included rosacea classification, triggers, quality of life, histopathology, treatment selection, long-term management, and maintenance strategies. Inclusion criteria were full text articles published in English that mentioned rosacea. References were selected on the basis of relevance, publication date, and methodological rigor. Clinical trials and systematic literature reviews were prioritized; however, given the lack of literature for rarer subtypes of rosacea, case reports were utilized. This was not a systematic or exhaustive review of the literature.

Ethical Approval

This article does not involve any new studies with human participants or animals conducted by the authors. Written informed consent was obtained from all patients featured in the clinical case studies for the publication of any potentially identifiable data or images contained in this article.

A Step-by-Step Longitudinal Pathway

To provide an overview of the longitudinal pathway for rosacea management, a simplified pathway (Fig. 1) has been developed to address each step of rosacea management—from patient self-management and entry into the medical pathway, through to maintenance of long-term treatment. It is advised that HCPs review, assess, and modify management on the basis of trigger assessment, comorbidities, determination of features, and relevant impacts. Patient progress points at each step aim to assist with the clinical decision-making, navigating assessments, and patient discussions. Further guidance is included in the final stage of the pathway, with suggestions for tools, investigations, guidelines, and patient questionnaires to be employed to help reach these clinical decisions and aim for successful rosacea management.

Fig. 1.

The Rosacea–Expert Advice on Combined and Holistic (REACH) longitudinal rosacea journey with patient progress points [7]. AARS American Acne and Rosacea Society, DLQI Dermatology Life Quality Index, IGA Investigator’s Global Assessment, NRS National Rosacea Society, OTC over-the-counter, PSA patient self-assessment, QoL quality of life, ROSCO ROSacea COnsensus

Patient Progress Point A: Self-Management and Entry into the Medical Pathway

The first step during consultations, prior to diagnosis, is establishing the patient profile. It is worth investing time and giving careful consideration at this point to avoid misdiagnosis and suboptimal treatment.

Combining patient self-assessments of their features, such as a patient’s Self‐Assessment and Subject Self‐Assessment [7], with the Dermatology Life Quality Index [8]—potentially as a preappointment questionnaire (via email and completed prior to their consultation)—or the 4-question High Burden Questionnaire at baseline [9], is useful as part of a standardized dermatology triage.

It is important to understand when a patient’s features started and if they have possible triggers (such as stress, sunlight exposure, heat, alcohol, certain (spicy) foods, new or existing medications, a family history, previous dermatoses, or hormonal changes) [10, 11]. Recent research indicates that genetic and environmental factors can trigger and aggravate rosacea through dysregulation of the innate and adaptive immune systems [10] (Fig. 2). Understanding the patient’s exposure to these factors can support HCPs in building a diagnosis and assessing the severity.

Fig. 2.

Rosacea risk and trigger factors [3, 10, 11]. CGRP calcitonin gene-related peptide, ET1 endothelin 1, MMP matrix metalloproteinase, NO nitric oxide, PCAP pituitary adenylate cyclase-activating polypeptide, SP substance P, TNFα tumor necrosis factor alpha, TRPV transient receptor potential vanilloid, VEGF vascular endothelial growth factor

A complete medical history may provide insights into possible comorbidities (and previous treatments), as recent reports have shown a significant association between rosacea and cardiovascular, gastrointestinal, autoimmune, and neurological diseases—all of which could affect patient morbidity and mortality [12]. Close attention to all presenting features may alert the clinician to the possibility that the patient may have more than one dermatosis, see “Multiple Features and Combination Treatments”.

Patient Progress Point B: Diagnosis

Symptomology, Clinical Features, and Comorbidities

The subtype-based classification proposed by the NRS 20 years ago [13], although useful, had limitations (Fig. 3). It has since been superseded by a more patient-focused approach, aligning with the latest clinical research and experience (Fig. 3) [1–5].

Fig. 3.

Evolution of NRS subtype-based classification [13] to current ROSCO phenotype-based classification of rosacea and its variants [1–5]. NRS National Rosacea Society, ROSCO ROSacea COnsensus

This transition to a phenotype approach proposed by the ROSCO expert panel [1–3] (Fig. 3), and subsequently by the NRS, recommends rosacea diagnosis and management according to patient presentation of disease features, rather than being constrained by predetermined subtypes. It is recommended that one of the diagnostic features and at least two of the major features are necessary for the diagnosis of rosacea.

A useful table describing common cutaneous features of rosacea forms part of the ROSCO 2019 update [1]. This covers diagnostic features (phymatous changes, persistent erythema aggravated by trigger factors), major features (flushing/transient erythema, papules and pustules, telangiectasia), and minor features (burning, stinging, dryness, edema) [1]. Dermatologists are encouraged to use the most recent guidelines [1–5] to identify the patient’s most problematic symptoms or sequelae (e.g., is it erythema, flushing, papules or pustules, itching, skin-thickening, telangiectasia, ocular rosacea, or other symptoms?).

As rosacea is phenotypically heterogeneous, patients might display several signs and symptoms. Treatments should be tailored to each patient [1–5]. HCPs are advised not to underestimate so-called invisible symptoms of rosacea, such as burning and stinging. Certain therapies available for rosacea can treat beyond the visible rosacea features, targeting underlying inflammation and microbiological causes [14].

More recently, rosacea has been linked to multiple comorbidities, including autoimmune conditions, gastrointestinal disorders, malignancies, cardiovascular disease, depression, migraines, dementia, and Parkinson’s disease [12]. While awareness of these comorbidities is important, it is worth noting that the observed associations are statistical in nature, and the directionality and causality remain uncertain [12]. Guidance on common comorbidities is provided in Fig. 4.

Fig. 4.

Common comorbidities in rosacea and screening considerations [12, 15]. Figure abridged from Haber and El Gemayel, 2018 [12]. BMI body mass index, CVD cardiovascular disease, HbA1c glycated hemoglobin

The developing concept of the gut–skin axis, and its involvement in the pathogenesis of many chronic inflammatory diseases, asserts that gastrointestinal health affects the skin homeostasis and allostasis through multifaceted interactions between the immune, metabolic, and nervous systems [15]. As a major regulator of this axis, the gut microbiome is strongly implicated, specifically regarding bidirectional modulation between the gut microbiome and host immunity [15].

Rosacea Triggers and Psychological Impact

Genetic and environmental factors can exacerbate or trigger rosacea partly through the release of neuropeptides, which can lead to the development of rosacea lesions [10]. The REACH GSC advises that trigger avoidance should be approached with sensitivity, recognizing that for some patients, the burden of restrictions can outweigh the burden of the disease itself; however, avoiding triggers during disease flares or exacerbations is still recommended. That said, when patient improvement is seen, it is worth examining whether it coincides with triggers being avoided, minimized, or removed. The REACH GSC highlighted certain treatments may act as triggers for some patients and overuse of steroids, when self-managing rosacea, can present problems.

Discerning how rosacea features might affect a patient’s quality of life (QoL) remains an important line of inquiry, and the better understanding an HCP has of their patient’s disease state, the better the opportunity for individualized treatment plans, maintenance, and successful outcomes. Evidence has shown that patients with rosacea have an increased risk of developing depression and anxiety, and certain rosacea features, especially erythema and flushing, may be particularly debilitating [16]. Effective treatment of clinical features brings significant improvement in psychological features; nonetheless, psychological support should be made available if thought beneficial for the patient [16]. The need to cleanse, treat, moisturize, and protect (CTMP) has been emphasized in the literature, where patients achieved greater success with combination treatments when actively using cleansers, moisturizers, and sunscreen alongside their treatment [4].

Rosacea is often characterized by dry, easily irritated, sometimes sensitive skin, where a disrupted skin barrier has increased trans-epidermal water loss and facilitated penetration of potential irritants or allergens [17]. Dermatologists should be aware that sensitive skin syndrome is not an immunological disorder but is related to alterations of the dermal nervous system (e.g., involvement of unmyelinated C-fibers and of transient receptor potential of the vanilloid subtype [TRPV] channels), and in certain subgroups, psychosocial factors (e.g., stress) might be relevant [18, 19]. The Sensitive Scale-10 is a tool to better define and assess sensitive skin syndrome and allows a comprehensive evaluation of dermocosmetic skincare products over time on key parameters relating to skin sensitivity [19, 20]. A total of 2966 patients presenting with sensitive skin were included in a study from 11 countries to validate the Sensitive Scale-10 diagnostic tool worldwide in patients presenting with sensitive skin, including patients with rosacea (9%) [20]. The study concluded the Sensitive Scale-10 was the first to measure the severity of skin sensitivity and then enable the measurement of variations pre- and post-treatment [20].

Considering Variation

Rosacea is under-recognized, underdiagnosed, and more difficult to discern in skin of color. For patients with Fitzpatrick skin types IV–VI, rosacea may well manifest/appear differently, with erythema being difficult to detect [21] (Fig. 5). In these cases, a full medical history considering family history and any prior history of acne diagnosis, as well as following the ROSCO/AARS/NRS diagnostic criteria, are advised to aid in deciding the most appropriate treatment selection [1–5].

Fig. 5.

Case study examples of rosacea in skin of color, skin phototype IV. A 28-year-old male of skin phototype IV complained of persistent facial erythema with papules and pustules. Patient reported facial erythema since childhood with seborrheic dermatitis and recent failed acne treatments. (i) In June 2023, he was commenced on isotretinoin 10 mg once daily, azithromycin 500 mg 3×/week for 6 weeks, and azelaic acid cream 15% before bedtime. Desonide cream 0.05% prescribed as needed for flares of seborrheic dermatitis along with regular use of mild cleanser, hydrating moisturizer, and silicone-based sunscreen. (ii) In October 2023, erythema, facial edema, and papules and pustules improved dramatically and isotretinoin 10 mg was reduced to 2 ×/week for a further 2 months. Azelaic acid cream 15% was maintained before bedtime. Daily sunscreen, mild cleanser, and hydrating moisturizer continued throughout. Images taken using 3DLifeViz mini by QuantifiCare (Biot, France). Images courtesy of Dr Johannes Dayrit with patient’s consent

Ocular manifestations of rosacea, such as lid margin telangiectasia, blepharitis, keratitis, conjunctivitis, and anterior uveitis are commonly overlooked. As eye health and vision might be affected, ophthalmological referral should be sought for all but mild forms of ocular rosacea [1, 2]. The ROSCO recommendations provide helpful information for dermatologists in deciding the severity of ocular symptoms [1].

Phymatous rosacea should be assessed according to both its stage of development (early or fibrotic), the level of facial edema, and the extent of inflammation (active or burnt out), as treatment will differ accordingly [1, 4]. Features include erythema, thickening of the skin, irregular surface nodularities, and enlargement of the pilosebaceous poral orifices (in rhinophyma) (Fig. 6). It is worth examining beyond the nasal region as it may occur on the cheek, nose (rhinophyma), chin (gnatophyma), forehead (metophyma), periorbital region (blepharophyma), or ear (otophyma) [22]. It is relevant to mention Morbihan’s disease here—a rare condition and complication of rosacea—that is characterized by chronic and persistent erythematous solid edema localized on the face, which is frequently treatment-refractory [23].

Fig. 6.

Case study example of mild rhinophyma. A 59-year-old male with a 15-year history of rosacea with mild rhinophyma. Previous doxycycline treatment (50–100 mg/day, 6–8-month treatment periods) for the past 10 years had initially controlled inflammatory symptoms (erythema, papules, and pustules) but had become increasingly ineffective. His doxycycline was ceased and he was switched to isotretinoin, 20 mg/day, for 4 weeks, reducing to 10 mg/day. He was commenced on a skincare regimen, including a cream-based cleanser at night followed by a simple hydrating moisturizer, with a high sun protection factor broad-spectrum sunscreen every morning. The images above show results at (i) 12 months maintaining skincare and 10 mg isotretinoin; and (ii) 18 months with continued isotretinoin and pulsed dye laser over the nose cheeks and chin, showing excellent control of papules and pustules, and dramatic shrinking of nasal swelling. Images courtesy of Dr Belinda Welsh with patient’s consent

Granulomatous rosacea is a clinically distinct form of rosacea where patients present with firm brown, yellow, red, or flesh-colored papules or nodules on the cheeks or around the eyes, nose or mouth on relatively healthy-looking skin [24, 25]. Histological differentiation may be needed, typified by noncaseating granulomas, which are seen in the superficial and mid dermis [24] (Fig. 7).

Fig. 7.

Case study of granulomatous rosacea. A 38-year-old female with a 7-year history of diffuse facial erythema, flushing, sensitivity, with periods of exacerbations and remissions, but no previous medical treatment. Initially appearing after the birth of her first child and worsening 3 years later after the birth of her second child. Condition possibly triggered or aggravated after using a home microdermabrasion machine. Clinically diffuse and perifollicular erythema papules and follicular micropustules extending to the lateral cheeks with associated mild melasma. The lateral follicular micropustules suggest possible coexistent pityrosporum folliculitis. Biopsy revealed upper dermal telangiectasia and perivascular lymphoplasmacytic inflammation with small perivascular and appendageal granulomas. Commenced on doxycycline 100 mg but ceased after 2 weeks due to indigestion and headaches, moved to ivermectin 1% cream. Commenced on isotretinoin 10 mg per day for 4 months, then 10 mg 3 × per week for a further 8 months. Daily sunscreen, night cleanser, and moisturizer as skincare throughout. Excellent clinical response but took many months to clear. Images courtesy of Dr Belinda Welsh with patient’s consent

Scalp involvement of rosacea is a rare diagnosis, seldom reported in literature. It poses a diagnostic challenge owing to its atypical presentation and the possibility of being associated solely with mild facial lesions. Primarily affecting males, clinical presentation includes erythema and sometimes papules and pustules and peripilar scaling (resembling that found in lichen planopilaris) [26, 27].

Rarer variants of rosacea have been recorded, such as neurogenic rosacea that has prominent neurological symptoms, including severe flushing and burning, stinging, and dysthesias, and does not respond well to conventional therapy [28, 29].

Microbiology and Histopathological Considerations

It has been well documented that, in genetically susceptible individuals, Demodex mites play a central involvement in rosacea pathophysiology [30–33]. From a diagnosis and treatment perspective, in some patients with rosacea, eradication of Demodex appears to alleviate rosacea features—it is assumed by preventing the formation of proinflammatory cytokines [31].

Histological results can provide further insights into the disease state of the patient, which can depend on the rosacea subtype under study (e.g., papulopustular or erythematotelangiectatic area) [14, 33, 34]. Although histopathological findings are broadly similar across rosacea phenotypes, subtle variations may be observed depending on inflammatory intensity and the presence of Demodex-associated changes [14, 34]. Owing to its invasive nature, biopsy is seldom required.

Patient Progress Point C: Treatment Selection

Foundational Skincare, Trigger Avoidance, Sensitive Skin Considerations, and Dietary Support

It is important to educate patients on the therapeutic dimension of skincare in rosacea. Indeed, skincare is integral to successful rosacea management prior to, and alongside, any prescribed treatment or intervention [35, 36]. The 2023 consensus recommends utilization of a consistent cleansing, moisturizing, and photoprotection holistic skincare routine as a tool for HCPs to encourage greater patient compliance and increase likelihood of success of treatments [37]. Using nonirritating or nonfragranced moisturizers with minimalist formulations to reinforce the skin barrier is recommended. Daily sun protection is imperative as ultraviolet light is not only a risk factor for skin cancer, but a significant trigger for many patients with rosacea [36, 38]. It is of note that disease morphology can alter or be impacted by a patient’s treatment, for example, existing use of corticosteroids.

Although not strictly a treatment, there is early evidence that probiotics may play a role in rosacea management as a potential adjunctive to treatment. Therapeutic use of probiotics is supported by their activity in neutralizing gut dysbiosis through the promotion of a healthier gastrointestinal microbial balance, potentially helping to reduce systemic inflammation and improve skin conditions [39].

Treatment Type, Duration, and Goal Setting

For easy reference, a refreshed version of the ROSCO 2019 treatment algorithm [1] is included in Fig. 8; however, as well as phenotype-based treatment selection, optimal goal setting is an important factor during treatment selection. It is critical to establish the following: what medications are available and affordable to patients? What rosacea features bother them the most? What medications are preferred by them? What is their treatment goal? Are they able to adhere to longer-term maintenance? When formulating a rosacea treatment plan, the application or type of medication, the potential benefits of using combination treatments, and the treatment duration should be reviewed with patients. The need for long-term treatment, adherence, and maintenance to optimize the length of remission and QoL should be highlighted [6].

Fig. 8.

Updated ROSacea COnsensus treatment recommendations [1]. ^†Persistent centrofacial erythema associated with periodic intensification by potential trigger factors. ^‡There is limited evidence to support the use of topical alpha-adrenergic-modulating agents or oral beta-blockers for treatment of flushing/transient erythema. However, clinical experience suggests that they could be considered in certain situations. ^§Not all products or indications are licensed in every country and may be subject to further local variations. For specific product information, the local label should always be consulted. Doxycycline 40 mg MR is superior to placebo; doxycycline 40 mg MR is noninferior to doxycycline 100 mg. No inference possible from indirect comparison. ^¶Use of IPL and vascular lasers in darker skin phototypes may require consideration by an HCP with experience in this situation. ^††For example, pulsed-dye laser and 532-nm KTP laser. Figure abridged from Schaller et al. Br J Dermatol, 2020 [1]. HCP healthcare professional, IPL intense pulsed light, KTP potassium titanyl phosphate, MOD moderate, MR modified release, SEV severe

Building on the updated ROSCO treatment recommendations, there are additions to the topical treatment armamentarium that warrant inclusion. Micro-encapsulated benzoyl peroxide cream (5%) and minocycline foam (1.5%) for papulopustular rosacea have both demonstrated efficacy and safety and are supported by the United States Food and Drug Administration [40, 41].

Topical treatments are often the initial treatment in rosacea and have shown to be very effective, however they can take several weeks to yield appreciable improvements and rosacea flare-ups can wax and wane. Exact instruction on application, treatment areas and amounts, and appropriate expectations for treatment results/outcomes should be discussed with patients to encourage adherence [6, 42].

Although systemic treatments are frequently reserved for more severe cases of rosacea, in the instance of inadequate response or intolerability of topicals, each patient’s personal circumstance and preference should be given due consideration when selecting the most appropriate therapeutic course of action [6, 42]. A modified-release subantibiotic dose of doxycycline has been studied and approved for use in moderate-to-severe rosacea, with 52 weeks safety data supporting its use in individuals who benefit from an oral medication [43].

Referring to established guidelines, consensus and reviews, guided by the patient’s values, preferences and presenting rosacea features, apparent phenotype and insights on treating to clear, will inform treatment selection [1–5].

Multiple Features and Combination Treatments

The REACH GSC advises giving greater attention to the frequent presentation of multiple, overlapping features of rosacea. This can help direct feature-targeted treatment decisions including the role or benefit of combination treatments [1, 5]. Cribier [44] asserts that different features of rosacea may require unique, targeted treatment. Tackling vascular changes, flushing, innate immunity or neurovascular components, for example, may require multiple treatment agents/modalities. Taking a combination or multimodal approach for patients with severe disease can be effective, particularly when there is an inflammatory element alongside targeting the repair and protection of the skin barrier [45], (Fig. 9).

Fig. 9.

Case study of multiple features requiring long-term and combination therapy. A 17-year-old female presenting with papules and pustules and ocular symptoms (blepharitis, chalazia, and corneal neovascularization) for several years. Ophthalmological referrals and multiple operations for chalazia and severe blepharoconjunctivitis confirmed. Ophthalmic topical therapy (cyclosporine, dexamethasone, tetracycline, ofloxacin) and lid margin hygiene (lipid-containing artificial tears). Treatment plan as follows. (i) At baseline, 100 mg doxycycline initially and topical metronidazole gel. (ii) At week 13, switched to doxycycline 40 mg MR and continued metronidazole gel. (iii) After 6 months, switched from metronidazole gel to ivermectin cream, brimonidine gel as required. (iv) 10-month results shown. (v) After 13 months, doxycycline 40 mg modified release stopped. For maintenance therapy, ivermectin cream regularly and brimonidine gel as required. Images courtesy of Professor Martin Schaller with patient’s consent

Patient Satisfaction

Regular monitoring is important, particularly after initial rosacea diagnosis, as is questioning the patient with regards to their satisfaction with treatment and their QoL. The HCP should maintain vigilance for the potential development of new rosacea features. Less frequent reviews or check-ups are necessary once a patient achieves symptom control (clear or almost clear) to discuss their expectations (aim towards achieving clear), but the patient should feel empowered to monitor their symptoms and discuss with their HCP should any deterioration occur. Smartphone technologies are available to support with analysis of erythema and roughness of the skin using white-balance and color-correction technology [46].

If symptom deterioration occurs, it may not be as a direct result of ineffective treatment; other factors such as nonadherence, skin irritation experienced with topical agents, incorrect treatment application, or trigger exposure might play a role. It is worthwhile exploring whether the current treatment application or type is still suitable for the patient to maintain. Understanding whether there has been recent exposure to triggers, such as stress, sunlight, allergens, or chemicals can be helpful, as well as ascertaining whether the patient is supporting their treatment with foundational or holistic skincare. If there are safety or tolerability concerns, the REACH GSC recommends that the frequency of follow-up be increased.

Progress Point D: Maintenance

Rosacea is a chronic condition and maintenance therapy is advised, as it may well be important for longer-term symptom control. Although data are lacking in this area, it is the experience of the GSC that using the minimum treatment required to attain and then maintain clear skin is ideal [2]. Some longer-term studies (Table 1) have shown that once patients reach clear skin, certain treatment modalities can maintain clinical remission for several months [6].

Table 1.

Long-term studies for rosacea treatment

Author, year	Study design	Treatment intervention	Patient population	Duration	Objective	Outcomes measured
Stein Gold et al., 2014 [47]	Phase 3 trial (two 40-week extension studies)	IVM 1% cream	Papulopustular rosacea	52 weeks	To assess the long-term safety of IVM 1% cream versus azelaic acid 15% gel	Incidence of AEs and percentage of subjects with IGA scores of clear or almost clear compared with baseline
Draelos et al., 2018 [48]	Open-label trial	Oxymetazoline	Rosacea patients with moderate-to-severe persistent erythema	52 weeks	To examine the long-term safety and efficacy of oxymetazoline cream 1%	Incidence of treatment emergent AEs and improvements in Clinician Erythema Assessment and Subject Self-Assessment scores
Anderson et al., 2017 [50]	Literature review: Phase 2, 3, and open-label studies	Brimonidine topical gel 0.33%	Rosacea	Typically limited to 52-week follow-up	To review the current literature regarding safety, efficacy, and patient acceptability of brimonidine 0.33% gel	Incidence of AEs and improvements in facial erythema as assessed by Clinician Erythema Assessment and Patient Self-assessment tools
Del Rosso et al., 2022 [43]	Two-part study: i) Open-label 12-week ii) Multicenter, randomized, double-blind, placebo-controlled 40-week trial	i) SDD40 and topical metronidazole gel 1% ii) SDD40	Moderate or severe inflammatory lesions (papules and pustules) of rosacea	52 weeks	To assess relapse and efficacy during long-term use of SDD40 versus placebo	Relapse defined as a return to baseline IGA scores or lesion count

AE adverse event, IGA Investigator’s Global Assessment, IVM ivermectin, SDD₄₀ subantibiotic dose oral doxycycline 40 mg modified release

Ivermectin

Two 40-week extension studies of phase 3 trials in ivermectin (IVM) 1% cream versus azelaic acid (AzA) 15% gel were conducted in patients with papulopustular rosacea (PPR). IVM 1% cream presented safe throughout the study with a lower incidence of related adverse events compared with AzA 15% gel. IVM 1% continued to be efficacious during the 40-week extension studies, with a higher percentage of subjects with Investigator’s Global Assessment (IGA) scores of “clear” or “almost clear” at the end of the study compared with baseline. These data support the use of IVM 1% cream as a long-term therapy for PPR, with safety and efficacy demonstrated for up to 52 weeks of total treatment [47].

Oxymetazoline

In the REVEAL trial, patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events, skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) composite score at 3 and 6 h after the dose on day 1, and at weeks 4, 26, and 52. At 52 weeks, the percentage of patients achieving a 2-grade or greater composition improvement from baseline in CEA and SSA scores at 3 and 6 h following a dose, was 36.7% and 43.4%, respectively. Fewer than 1% of patients experienced a rebound effect following treatment cessation [48]. An additional review found oxymetazoline effective for the treatment of persistent facial erythema of rosacea without a significant risk of apparent worsening of facial erythema and rebound, or the paradoxical erythema sometimes associated with topical brimonidine [49].

Brimonidine

Brimonidine topical gel 0.33% was efficacious compared with vehicle gel for moderate-to-severe persistent facial erythema of rosacea in phase 2, phase 3 and open-label studies, both as monotherapy and in conjunction with other acne and rosacea medications. Concentrations of 0.07%, 0.18%, and 0.5% were compared against vehicle gel in both one-time and daily applications for 4 weeks. In the one-time dosing trial, improvement in facial erythema was correlated with increasing brimonidine tartrate concentration. After application of brimonidine tartrate 0.5% once daily for 4 weeks, there was superior improvement in erythema compared with lower concentrations and vehicle gel. The short-term and long-term erythema control offered by brimonidine tartrate gel has shown advantages for patients with rosacea; however, the relatively high rate of adverse reactions and potentially significant rebound must also be appropriately conveyed to patients [50].

Modified Release Doxycycline

Topical metronidazole and subantibiotic dose doxycycline (SDD₄₀), administered as a once-daily 40 mg modified-release capsule, have been reported to be an effective combination therapy for a flare of PPR. To expand on this evidence, a two-part study examined the potential of extending duration of remission following successful therapy to control a flare. The initial study was a multicenter, open-label, 12-week study in which adults with moderate or severe inflammatory lesions (papules and pustules) of rosacea received SDD₄₀ and topical metronidazole gel 1%. The second study was a multicenter, randomized, double-blind, placebo-controlled, 40-week study in which successfully treated subjects received once-daily SDD₄₀ or placebo capsules. The study’s primary objective assessed relapse and efficacy during long-term use of SDD₄₀ versus placebo. Following 52 weeks of once-daily treatment, SDD₄₀ significantly reduced the relapse rate and inflammatory lesion counts in subjects with moderate-to-severe inflammatory rosacea [43].

REACH GSC Clinical Experience and Recent Therapeutic Investigations

This section presents anecdotal insights from REACH GSC members on their approaches to maintenance therapy for patients with rosacea. It was unanimously agreed that the maintenance approach and duration is dependent on the severity of a patient’s rosacea, along with success of prior treatment, and the duration of features or symptoms. For patients presenting with late-onset rosacea, maintenance is more important and GSC members advise using topical treatments, perhaps every other day to maintain clear skin. Oral or systemic medicine can be supplied at review and used on an ad-hoc basis.

There was also consensus among GSC members surrounding physical therapies. Light-based therapies, such as vascular laser and the more recently studied 577 nm pro-yellow laser [51], can act as an important tool, not only for initial improvement in features such as redness, telangiectasia, flushing, and inflammation, but also to help reduce Demodex densities [52]. The GSC members discussed how, given the described improvements in features, such therapies may also be a patient-driven option for long-term maintenance.

All GSC members were keen to highlight that an effective daily skincare regimen and sunscreen application (CTMP) remains a crucial part of rosacea management during long-term maintenance.

In line with a recent Brazilian- and USA-based dermatologist consensus panel, the maintenance treatment phase (beginning once the patient achieves IGA 0 or 1 during the initial active phase) should be considered for at least a 9-month period after remission [53].

Explaining that patients play a critical role in maintenance and extending remission is encouraged, through correct treatment application, adherence, trigger avoidance/minimization, and use of supportive skincare (including sun protection). Lifelong use of daily sunscreen and appropriate skincare can not only prevent flares but also prevent precancerous actinic keratosis and keratinocyte skin cancers, as sunlight is a major trigger for both rosacea and skin cancer [2]. It is hypothesized that limiting flares and recurrences of rosacea may lessen the development of some features of rosacea (i.e., telangiectasia, persistent background erythema, phyma).

It is imperative to better understand treatment maintenance; further clinical studies and real-world evidence will expand our knowledge, advance clinical practice, and improve patient outcomes.

Conclusions

Rosacea can be a burden on the lives of those affected, reducing QoL both from the discomfort of symptoms and concern about the skin’s appearance. A clinical evaluation to discern all the clinical features of rosacea present in each patient is a requirement. Clear and sensitive patient communication is imperative to determine the overriding signs and symptoms, their impact on QoL, potential comorbidities and achievable outcomes [1].

HCPs can empower their patients with informed, shared decision-making through discussions on treatment selection and correct application, trigger avoidance, adherence, and the necessity to support treatment regimens with foundational skincare and sun protection. Managing patient expectations concerning long-term management and therapeutic control of rosacea should be treated carefully, emphasizing that the condition is chronic, yet manageable. It is particularly important for patients to feel that they can influence the fate of their disease on their own [1].

The REACH GSC has compiled this framework to help remind and prompt HCPs to have those discussions with their patients, and the considerations to keep in mind at each stage of rosacea management. Existing guidance and consensus papers have been signposted to aid in the diagnosis and treatment of rosacea, supported by clinical case studies provided by the GSC members for more uncommon or difficult-to-discern types of rosacea.

Treatment Recommendations and Clinical Case Studies

Where certain agents have not yet been reviewed by the ROSCO panel as a whole they do not appear in Fig. 8, but are alluded to, if approved for treatment of rosacea, elsewhere in the text. Although off-label use of treatments may be adopted by the REACH members, unless treatments have been approved for the indication of rosacea, they are not covered within this manuscript.

The agents or therapies listed in the clinical case studies are at the discretion of the REACH panel member supplying the case study and are included for full disclosure of treatment approach, although a consensus recommendation for this modality may not yet be supported.

Author Contributions

Martin Schaller and Linda Stein Gold led the manuscript development. All authors contributed to the drafting and revision of the manuscript, which includes Martin Schaller, Belinda Welsh, Giuseppe Micali, Jerry Tan, James Del Rosso, Julie Harper, Thomas Dirschka, Soyun Cho, Luiz MC Almeida, Khen Kon, Wioletta Barańska-Rybak, Johannes Dayrit, and Linda Stein Gold. Case studies were provided by Johannes Dayrit, Belinda Welsh, and Martin Schaller.

Funding

This paper was initiated and funded, including the journal’s Rapid Service Fee, by Galderma SA, Switzerland.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Martin Schaller reports grants and personal fees from Galderma, personal fees from Abbvie, personal fees from Bayer Healthcare, personal fees from InfectoPharm, personal fees from Lilly, outside of the submitted work. Belinda Welsh reports advisory and speaker roles for Galderma and Candela. Giuseppe Micali reports advisory speaker roles for Eli Lilly, UCB, Pfizer and Incyte. Jerry Tan reports advisory, consultant and speaker roles for Avene, Bausch, Boots Walgreens, Galderma, L’Oreal and Sun Pharma. James Del Rosso reports clinical research investigator*, consultancy/ advisory^ and speaker^# roles for AbbVie^^#, Aclaris*^^#, Almirall*, Amgen (Celgene)*^^#, Anaptys Bio*, Apogee Therapeutics*, Arcutis*^, Aslan*^, Athenex*, Bausch (Ortho Dermatology)*^^#, Beiersdorf^^#, Biofrontera^*, Biopharmx*^, Biorasi*, Blue Creek^, Botanix*, Bristol Myers Squibb*^^#, Cage Bio*, Cara Therapeutics*, Cassiopea*^, Dermata^ Dermavant^*, Encore^*, EPI Health*^^#, Evommune*^, Ferndale^*, Galderma*^^#, Genentech*^#,Incyte*^^#, Janssen*, Johnson & Johnson^, La Roche Posay^, LEO Pharma*^^#, Lilly*^^#, L’Oréal^, MC2^, Moonlake*, Nektar*, Novan *^, Nutrafol^, Pfizer*^^#, Ralexar*, RBC Consultants^, Regeneron*^^#, Sanofi-Genzyme^*, Sente^, Solgel*^, Sonoma (Intraderm)^, Sun Pharma*^^#, Takeda*^, UCB*^^#, Verrica^* and Vyne^#. Julie Harper reports advisory and speaker roles for Almirall, Arcutis Biotherapeutics, Bioderma, Beiersdorf, Bubble Beauty Inc, Cutera, Galderma, Journey Medical Corporation, L’Oréal, Nutrafol, Ortho Dermatologics, Pelthos Therapeutics, Sagimet Biosciences, Sanofi and Sun Pharma. Thomas Dirschka reports research support for Abbvie, Almirall, Biofrontera, Damae, Emblation, Galderma, Intros, ISDIN, La Roche Posay, L ‘Óreal, Mylan, Nordberg, Olistic, Schulze & Böhm GmbH, Scibase S.A., Smartinmedia AG, Speclipse, and Vichy. Lectures for Aesclepion, Almirall, Biofrontera, Damae, Dr. August Wolff, Galderma, GSK, Infectopharm, Intros, Janssen-Cilag, Leo, Louis Widmer, Mylan, Neracare, Nordberg, Novartis, Pierre Fabre, Pfizer, Riemser, Speclipse, and UCB. Member of advisory boards for Almirall, Beiersdorf, Biofrontera, GSK, Dr. Pfleger, Galderma, Janssen-Cilag, Leo, Mylan, Neracare, Nordberg, Novartis, Pierre Fabre, Scibase, Smart In Media AG, and Vichy. Soyun Cho has nothing to disclose. Luiz MC Almeida has nothing to disclose. Wioletta Barańska-Rybak reports advisory and speaker roles for Galderma. Johannes Dayrit reports speaker roles for Isispharma. Linda Stein Gold reports advisory, investigator and speaker roles for Galderma, Almirall, Journey Medical Corporation, Ortho Dermatologics and Sun Pharma. Khen Kon is an employee of Galderma.

Ethical Approval

This article does not involve any new studies with human participants or animals conducted by the authors. Written informed consent was obtained from all patients featured in the clinical case studies for the publication of any potentially identifiable data or images.

Conception Statement

This framework was conceived and developed by the Rosacea–Expert Advice on Combined and Holistic approaches (REACH) Global Scientific Committee (GSC) across three meetings, which included Martin Schaller, Belinda Welsh, Giuseppe Micali, Jerry Tan, James Del Rosso, Julie Harper, Thomas Dirschka, Soyun Cho, Luiz MC Almeida, Wioletta Barańska-Rybak, Johannes Dayrit, and Linda Stein Gold.