The Management of Rosacea

US Pharm. 2024;49(5):35-38.

ABSTRACT: Rosacea is a chronic facial skin disorder that affects 5.5% of the global population, with higher rates in white individuals and women. Its etiology involves genetic, immune, microbial, and environmental factors. Diagnosis relies on clinical observation, and management aims to alleviate symptoms through lifestyle modifications, skin care, and pharmacotherapy. Treatment includes topical and oral therapies, as well as device therapy for certain features. Ocular involvement is common, requiring specialized care. Despite the lack of a cure, effective management strategies aim to improve patients’ quality of life.

Rosacea is a disorder of the facial skin that may be associated with disturbances on the forehead, cheeks, nose, and chin. It is a chronic, inflammatory disorder that is often characterized by periods of remission and exacerbations. In some cases, it may be associated with ocular manifestations. Rosacea’s conspicuous appearance may cause patients emotional ramifications, including depression or anxiety, and may interfere with social and occupational interactions.¹

Based on epidemiologic studies, the incidence rate of rosacea is 10% or higher in white individuals; however, a recent analysis of worldwide epidemiologic data estimated that rosacea may affect 5.5% of the global population.¹ It is more commonly diagnosed in women than in men. Onset may occur at any age, but rosacea typically occurs after age 30 years.² 

Pathophysiology and Etiology

The pathophysiology of rosacea is not completely understood, but it is thought that genetic and environmental factors contribute to its development and progression. There is debate regarding the varying subtypes of rosacea and a lack of consensus on whether they represent a spectrum of disease progression or if they are individual clinical entities. Emerging studies have shown that the diverse features of rosacea and its phenotypes may be due to a range of inflammation that is able to be detected both biochemically and histologically.³

Several factors are thought to contribute to the development of rosacea, including genetics, immune reactions, microorganisms, environmental factors, and neurovascular dysregulation. For example, ultraviolet light is known as a trigger, and it may also play a role in the etiology of the disease. Second, genetic predisposition for rosacea may exist. This is supported by the fact that patients with a family history of rosacea have a higher incidence of the disease. Specific human leukocyte antigen loci have been identified in patients with rosacea. Lastly, higher numbers of Demodex mites are seen on rosacea-affected skin, but it is unclear if this is a cause or consequence of rosacea.⁴

Diagnosis

Rosacea is diagnosed based on clinical observation and patient history. No definitive laboratory test is used for rosacea diagnosis. It is important to obtain a detailed patient history because some features may not be visible or present at the time of the patient’s visit.¹

 Per the 2019 update by the National Rosacea Society (NRS) Expert Committee, diagnosis is based on a standardized classification system comprised of diagnostic, major, and secondary features. The presence of one diagnostic feature or at least two major features is diagnostic of rosacea.¹

Diagnostic features include persistent facial redness and skin thickening. Persistent facial redness may resemble a blush or sunburn and is the most common individual sign of rosacea. Skin thickening is less common but may occur when the skin enlarges from excess tissue. This is most commonly seen on the nose and is known as rhinophyma.⁵              

The presence of at least two major signs is diagnostic of rosacea. Major signs include flushing described as a facial redness accompanied by a sense of heat, warmth, or burning; small solid-red bumps and/or pus-filled pimples plus burning and stinging; visible small blood vessels known as telangiectasia on the central face; and eye irritation in several forms, commonly known as ocular rosacea.⁵

Secondary signs and symptoms may appear with one or more of the diagnostic or major signs. They include facial burning or stinging, facial swelling, and facial dryness. In rare cases, signs and symptoms of rosacea may develop beyond the face and most commonly occur on the ears, neck, chest, or scalp.⁵  

Classification

In 2002, the NRS assembled an expert committee to develop a classification system and provide standard diagnostic critera to be used in research, data comparison, and clinical practice. This system was based on morphologic characteristics alone and was to provide a framework to be updated as new discoveries were made. An update was published by the NRS in 2017 due to the growing knowledge of rosacea’s pathophysiology.  The classification has since evolved from a division into distinct subtypes to a phenotype-based approach that views the various features of rosacea as manifestations of a continuous multivariate disease process.^1,2

Management

There is no cure for rosacea, but its features may be reduced or controlled with a range of therapies, including topical and oral pharmacotherapy, light devices, skin care, and lifestyle management.

Patient surveys have suggested that the psychosocial burden of rosacea may be substantial regardless of severity. When assessing treatment, providers should account for patients’ perception and acceptance of their facial appearance, including its impact on their emotional, social, and professional lives. This may be important in determining the level of therapy.¹

General Measures

Lifestyle modifications may be useful for the management of the cutaneous manifestations of rosacea. These include gentle skin care, sun protection, the use of nonirritating cosmetic products, and the avoidance of triggers that cause flushing.^6,7

Patients with rosacea may have rough, dry, or scaly skin; they may also experience increased skin sensitivity and have difficulty tolerating topical cosmetics, skin care products, and topical medications. It is not clear if the skin dryness and sensitivity are due to the inflammatory process of rosacea or if they occur because of the inflammatory process. The goal of skin care for patients with rosacea is to maintain the integrity of the skin barrier and avoid agents that may irritate the skin. Gentle skin care practices are an important component of rosacea management. Frequent skin moisturization can be beneficial, especially when using emollients, which can help repair and maintain the skin barrier.^1,8

Patients with rosacea should be advised to cleanse their face at least once daily with lukewarm water and a synthetic detergent or nonirritating cleanser. They should wash with their fingers and avoid harsh mechanical scrubbing. It is advised that patients let the face dry before applying topical therapy or any other products because stinging may occur more often when the skin is wet. Topical agents such as astringents, toners, and chemical exfoliating agents may irritate the skin, and patients should avoid these products.¹

Sun exposure plays an uncertain role in the pathogenesis of rosacea. It is recommended that patients apply sunscreen daily, making sure to use a broad-spectrum sunscreen with a sun protection factor of at least 30. The NRS guideline recommends the use of mineral inorganic products containing zinc oxide or titanium dioxide when possible. These mineral-based sunscreens provide physical protection instead of chemical protection, which may be irritating to the skin. They also do not produce heat as a byproduct. They work by reflecting and absorbing ultraviolet radiation. There are additional options, including micronized, nanoparticle, and clear formulations. These options are beneficial in patients with rosacea who have darker skin and for whom other formulations leave a chalky- white or gray appearance.¹

Cosmetics may be effective in reducing the appearance of redness, especially cosmetics with a green or yellow tint. However, patients should choose products that minimize irritation and avoid any products that cause itching, stinging, burning, or any other discomfort.¹

Potential triggers for flushing include alcohol, spicy foods, exercise, temperature extremes, sunlight, and medications. The degree of flushing in response to these stimuli is variable, and patients may have unique triggers for flushing. It can be helpful for patients to keep a diary of flushing episodes to identify potential associated factors and avoid triggers. When exposed to stimuli, patients can take practical measures to reduce flushing, such as applying cool compresses and transferring to cool environments.^1,6

Pharmacotherapy

The 2019 update by the NRS Expert Committee lists treatments to target specific features of patients with rosacea. This article does not provide a treatment protocol but offers a “menu of options” for rosacea management. Combination therapy is often necessary to target specific features of each patient with rosacea. Features of rosacea may appear in different combinations and at different times, but research has found that all appear to be manifestations of the same underlying inflammatory continuum. Any therapy, therefore, may prove to be working on an aspect of that continuum.¹

The recommendations from the global ROSacea COnsensus (ROSCO) panel from 2017 provide treatment options based on a phenotype-led algorithm that were updated in the 2019 ROSCO publication. Similarly to the NRS 2019 update, this guideline recommends first-line treatment choices based on patient presentation. However, it also subcategorizes first-line treatments based on symptom severity.^7,9

The FDA-approved topical therapies for inflammatory papules and/or pustules of rosacea include azelaic acid, ivermectin, metronidazole, and sodium sulfacetamide/sulfur. Doxycycline modified-release capsules are approved in a lower dosage than doxycycline used to treat infections. This modified-release capsule contains 30 mg of immediate-release and 10 mg of delayed-release beads. This formulation of doxycycline has been associated with fewer adverse effects, has not been associated with the development of bacterial resistance, and has shown to be safe for long-term use. Topical and oral therapies may be prescribed in combination, followed by long-term use of monotherapy to maintain remission.¹

Off-label antibiotics or retinoids may be used in cases of severe rosacea or when first-line treatments are inadequate. These agents may include tetracycline, doxycycline, minocycline, and oral isotretinoin.¹

The FDA-approved topical therapies for persistent facial erythema of rosacea in adults include brimonidine 0.33% gel and oxymetazoline hydrochloride 1% cream.¹ In some cases, certain drugs have been prescribed off-label to help control flushing. These include such agents as clonidine, antihistamines, nonsteroidal anti-inflammatory drugs, and beta-blockers.¹

Patients with rosacea often present with transient erythema, or flushing. Per the NRS guideline, the pharmacologic agents with the strongest data to treat transient flushing are topical ivermectin, brimonidine, or oxymetazoline, and oral carvedilol, clonidine, or propranolol. Similarly, the ROSCO 2019 guidelines recommend topical alpha-adrenergic agents. The ROSCO 2019 guidelines state that there is limited evidence to support the use of either of these therapies but that clinical experience suggests that they could be considered in certain situations. Nonpharmacologic therapy to help manage flushing includes lifestyle modifications such as avoiding potential triggers and skin care. Per the NRS guideline, device therapy may also be used, including intense pulsed light (IPL) and potassium titanyl phosphate.^7,9

Patients with rosacea may also experience persistent erythema. This may be a prominent and troubling feature for some individuals. Some postulate that flushing may contribute to the worsening of other features of rosacea. Per the NRS guideline, the pharmacologic agents with the strongest data to treat persistent erythema are topical brimonidine and oxymetazoline. Oral carvedilol, doxycycline (usual and lower dose), minocycline, and tetracycline may also be used. The ROSCO guidelines similarly recommend topical adrenergic agents, and device therapy may also be used. The NRS recommends IPL, pulsed dye laser, or potassium titanyl phosphate. The ROSCO guidelines also recommend IPL and vascular laser therapy.^1,7,9

Inflammatory papules and/or pustules may be present in rosacea. Most patients with mild-to-moderate disease can be managed with topical therapies. The NRS and ROSCO guidelines both recommend topical ivermectin, metronidazole, and azelaic acid as first-line therapies in mild-to-moderate disease. Systemic therapy is typically used in patients who fail to respond satisfactorily to topical agents or who present with numerous inflammatory lesions. Both guidelines recommend subantimicrobial doxycycline as a first-line agent. The ROSCO guidelines also list oral isotretinoin as an option for severe cases.

The NRS guideline recommends device therapy with IPL, pulsed dye laser, or potassium titanyl phosphate for the management of telangiectasia. The guideline also recommends topical retinoids but with less relative efficacy per the expert panel’s opinion. ROSCO 2019 recommends device therapy for management of telangiectasia, including electrodesiccation, IPL, and vascular laser.

Phymatous features are cutaneous, hypertrophic changes that most commonly affect the nose. Cutaneous changes include follicle dilation and irregular nodularity. The clinical course of these changes is uncertain, and there are limited data regarding early intervention for this manifestation.³ Both guidelines separate management of phymatous features into phyma that is clinically inflamed versus clinically not inflamed. For noninflamed phymas, the NRS recommends several device therapies, including carbon dioxide, erbium, cold steel, electrosurgery, or radiofrequency. The ROSCO guidelines also recommend all physical modalities.^1,7,9

For inflamed phymas, the NRS guideline recommends several agents. Some of these agents can be used in combination. Treatment may include topical retinoids, oral doxycycline (including subtherapeutic doxycycline), minocycline, tetracycline, azithromycin, and sulfamethoxazole/trimethoprim. It also recommends oral isotretinoin with a stronger expert recommendation. The ROSCO guidelines recommend oral doxycycline or oral isotretinoin.

Ocular Rosacea

Ocular manifestations occur in more than 50% of individuals with rosacea. They may occur before or in the absence of cutaneous features. Ocular rosacea may appear as a spectrum of disease and be related to underlying inflammation. Symptoms may include dryness, burning and stinging, light sensitivity, blurred vision, and foreign body sensation. In advanced disease, patients may present with chalazion affecting the eyelid. In severe cases, ocular rosacea may lead to corneal inflation and scarring, and conceivably, corneal perforation with loss of visual acuity.^1,7,9

Central components of treatment for ocular rosacea include eyelash hygiene, oral omega-3 supplementation, and topical azithromycin or calcineurin inhibitors. Eyelash hygiene involves applying warm compresses and cleansing eyelashes twice daily with baby shampoo on a wet washcloth. Patients may use antibiotic ointment to decrease the presence of bacteria and soften any collarettes, allowing easy removal by the patient during eyelash hygiene. Topical cyclosporine drops may be used to help decrease topical inflammation in these patients. An oral tetracycline may also be used.¹

1. Thiboutot D, Anderson R, Cook-Bolden F, et al. Standard management options for rosacea: the 2019 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2020;82(6):1501-1510.
2. Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78(1):148-155.
3. Nguyen C, Kuceki G, Birdsall M, et al. Rosacea: practical guidance and challenges for clinical management. Clin Cosmet Investig Dermatol. 2024;17:175-190.
4. Farshchian M, Daveluy S. Rosacea. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024.
5. National Rosacea Society. All about rosacea: signs & symptoms and treatment. www.rosacea.org/patients/all-about-rosacea. Accessed February 28, 2024.
6. Odom R, Dahl M, Dover J, et al. Standard management options for rosacea, part 2: options according to subtype. Cutis. 2009;84(2):97-104.
7. Schaller M, Almeida LMC, Bewley A, et al. Rosacea treatment update: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017;176(2):465-471.
8. Wilkin JK. Use of topical products for maintaining remission in rosacea. Arch Dermatol. 1999;135(1):79-80.
9. Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182(5):1269-1276.

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