Rosacea is a relapsing chronic inflammatory skin condition affecting 10% of the population or 3 million Canadians and is most commonly seen in Caucasian patients. Rosacea has a variety of presentations and signs can include:

• episodic flushing on the face with ocular sparing
• papules
• pustules
• telangiectases (broken capillaries)
• skin thickening of nose (rhinophyma), chin (gnathophyma), or forehead (metophyma).

Rosacea occurs mostly in adults with a peak incidence occurring in the fourth to seventh decades. Originally termed "adult acne", rosacea is a separate disorder and is distinguished from acne by the absence of comedones.  People of all races can get rosacea but it is most common in fair-skinned people of northern European, Celtic, or Dutch Ancestry.   Women are affected approximately two to three times more frequently than men, but cases in men are generally more severe and may result in complications such as rhinophyma.  A family history of rosacea is common.  Approximately 50% of patients develop eye problems.

Rosacea can lead to significant facial disfigurement, emotional suffering and serious ocular complications if left untreated. Rosacea has been found to negatively impact patients' quality of life by lowering self-esteem leading to patients avoiding public contact and cancelling work and social plans.  An increased prevalence of depression has been documented in rosacea patients. 

Pathophysiology of Rosacea                                                                                                             Rosacea is known to be triggered by various external stimuli which can vary substantially between patients. Triggers include:

• weather e.g. hot or cold temperature, sunlight, UV radiation, strong winds, excessive humidity
• emotional influences e.g. strong emotions, stress, anxiety
• heat-related triggers e.g. weather, saunas, baths
• physical exertion e.g. exercise, lifting
• beverages e.g. alcohol, hot drinks
• foods e.g. spicy food, liver, dairy products
• tobacco
• medications e.g. topical corticosteroids, vasodilators
• cosmetics

The pathophysiology of rosacea remains unknown, but various abnormalities have been detected in the vascular, neural, and inflammatory responses of patients. Dysregulation of thermal mechanisms has been demonstrated in rosacea patients including physiological responses at a lower threshold to heat. The evidence is mixed regarding the role of bacteria, specifically H. pylori in rosacea; H pylori may play a role in forming papulopustules and is prevalent in rosacea patients studied in Mediterranean countries. However treatments eradicating H. pylori have not consistently shown a clinical effect on rosacea symptoms. The successful treatment from antibiotics is thought to be from their anti-inflammatory properties.

The diagnosis of rosacea is a clinical diagnosis. Because of the variable presentations of rosacea, diagnostic criteria have been established based on primary and secondary features. 

Primary Features:   Rosacea typically affects the convex areas of the central face (cheeks, forehead, nose, and chin). Often the signs are transient and can occur independently of each other.

One or more of the following signs is indicative of rosacea: 

• flushing or transient erythema
• nontransient erythema for at least three months
• dome shaped red papules with or without pustules are typical. If comedones are present, consider acne as this represents a process unrelated to rosacea.
• telangiectasia (visible capillaries) are common but not necessary for a rosacea diagnosis.

Secondary features:       Patients with rosacea may have one or more of the following which usually occur as primary symptoms but can occur independently: 

• burning or stinging
• edema
• dry skin appearance
• plaques
• ocular manifestations
• phymatous changes i.e. thickening of the skin 

Because the pathophysiology is unclear for rosacea, the disease was categorized into four major subtypes to aid clinicians by highlighting which cluster of signs of presentation would benefit from specific therapeutic interventions. The subtypes are: erythematotelangiectatic, papulopustular, phymatous, and ocular. Except for phymatous rosacea where there can be progression to skin thickening and nodularities, rosacea is not found to be a progressive disease. 

The predominant sign of ETR is central facial flushing with periocular sparing which can be accompanied by burning or stinging. Occasionally, patients will have a permanent flush and may have mild facial edema. The erythematous areas of the face may appear rough with scaling or dryness due to chronic low grade dermatitis. Patients often report extremely sensitive skin and find the burning and stinging are exacerbated when topical agents are applied. 
 

Flushing in rosacea is different than flushing in response to embarrassment, exercise, or hot environments. 

Rosacea flushing:  

•  lasts at least 10 minutes
• accompanied by burning and stinging
• no sweating, light-headedness, or palpitations
• triggered by emotional stress, heat changes, alcohol, foods, exercise

Papulopustular rosacea is the classic presentation of rosacea.  Often patients are middle aged women who present with persistent or episodic central facial erythema with small papules and pustules.  Patients may also report burning and stinging. Telangiectasias may be present, but may be difficult to distinguish from the erythema. 
 

Phymatous rosacea is characterized by marked thickening of skin and irregular nodularities of the nose, chin, forehead, ears and/or eyelids. This subtype predominantly affects males.

The onset of ocular symptoms of rosacea can occur before, after, or in conjuction with the onset of the dermatologic symptoms of rosacea. Ocular symptoms peak in incidence during the sixth and seventh decades and men and women are equally affected.  Symptoms vary but may include: watery or bloodshot eyes (conjunctival hyperemia), foreign body sensation, dry eyes, tearing and itchy eyes.  Patients have also reported blurred vision and reduced visual acuity, photophobia and telangiectasias of the eyelids.  Styes and blepharitis can be common. If untreated, ocular rosacea can lead to loss of vision due complications including keratitis, corneal ulcers, and corneal infiltrates.

The ultimate goal of rosacea treatment is to control the disorder and minimize discomfort to patients. Management has four key elements and will vary depending on the subtype of rosacea: 

• trigger reduction
• antibiotic therapy (topical and oral)
• Laser and Intense Pulsed Light Therapy (IPL)
• skincare and camouflage

Trigger Reduction                                                                                                                                            As a chronic illness, patients will need to take an active role in management. Patients are encouraged to keep a diary to identify triggers for rosacea flares and avoid or minimize exposure to triggers accordingly.  Advice for trigger reduction includes:

Trigger Management Strategies

• hot or cold temperatures and sunlight.   Daily use of sunscreen with minimum SPF 15.
• Dimethicone or cyclomethicone (silicones) in sunscreens are best tolerated
• physical blockers such as titanium dioxide or zinc oxide are also generally well-tolerated
• cover up outdoors with light weight fabrics
• protect cheeks and face with scarf when cold or windy
• use air conditioning when hot and humid
• food and drink - identify and avoid triggering foods and drinks
• be aware of drink temperatures
• exercise for shorter, more frequent intervals
• exercise outdoors when temperatures are cooler (morning/evening)
• mist face with cool water when exercising indoors
• drugs (topical steroids, vasodilators) . Discuss other options with healthcare provider.
• stress  - try relaxation techniques including deep-breathing, visualization, and meditation
• gentle stretching to relax muscles
• cosmetics/cleansers  - avoid those with alcohol, witch hazel, menthol, peppermint, salicylic acid, eucalyptus oil, or clove oil

 When commencing antibiotic therapy, eight weeks is needed for an adequate trial of therapy.

Topical Therapies                                                                                                                                 Effective for ETR and PPR subtypes of rosacea, but use caution in patients with ETR as some patients can be sensitive to topical agents.                                          

Metronidazole gel: Metronidazole gel in 0.75% or 1% formulation treats inflammatory pustules, papules, and erythema.  Metronidazole 1% requires once daily application while metronidazole 0.75% requires twice daily application. Metronidazole 1% formulation includes niacinamide (vitamin B3), an agent with moisturizing and anti-redness properties. Side effects include stinging, burning, scaling, and moderate to severe dryness.

Sulfacetamide 10% and sulfur 5% combination: The sodium sulfacetamide has antibacterial properties and the sulfur is an antiseptic with keratolytic action. Effective for papules, pustules, and erythema. Common side effects include photosensitization, dryness and local irritation such as stinging, burning and itching. Patients with sulfa drug allergy are generally intolerant to this combination.

Azelaic Acid Azelaic acid 15% is effective in treating rosacea papules and pustules and reduces the severity of erythema. Effective against mild to moderate PPR and ETR. Azelaic acid can be used as twice daily as initial therapy. Azelaic acid is not commercially available in Canada, but pharmacists can prepare it. Side effects of azelaic acid are pruritus, burning, stinging, tingling, erythema, rash, dermatitis, peeling and irritation.

Tretinoin (Retinoid therapy) Topical tretinoin is effective in treating pustules and papules. The collagen remodeling is thought to be beneficial since collagen degeneration is observed in rosacea. However, tretinoin may worsen erythema. Tretinoin cream can increase sun sensitivity.

Oral Therapies

Antibiotics Tetracycline, minocycline, doxycycline, erythromycin and second generation macrolides, and metronidazole have all been demonstrated to be effective in treating pustules and papules but generally do not affect erythema. Effective against mild to moderate papulopustular and ocular rosacea.

Tetracycline is known to induce photosensitivity which is less of problem with minocycline. Gastrointestinal symptoms, yeast infections, and reduction in oral contraceptive therapy are possible side effects. Patients taking oral metronidazole must abstain from alcohol to avoid alcohol-induced headaches; this effect is not observed with topical metronidazole. Neuropathy is a rare side effect with oral metronidazole. Tetracyclines are mutagenic but other antibiotic classes are options during pregnancy and breast feeding.

 Isotretinoin is found to be effective in severe or persistent rosacea that does not respond to antibiotic therapy. Isotretinoin can be extremely drying to skin, eyes, and mucosa and side effects can include pruritus, dermatitis, myalgia, elevated liver enzymes and cholesterol. Routine monitoring of liver and cholesterol is required. Isotretinoin can be used for phymatous rosacea and low-dose isotretinoin is used occasionally for severe, antibiotic-resistant ocular rosacea.

Combination Oral and Topical Therapy Papulopustular and ocular rosacea require combination antibiotic therapy for one to three months. Oral therapy is continued until inflammatory lesions clear or twelve weeks, whichever occurs first. Topical therapy is continued as maintenance therapy to maintain remission.

Laser therapy is effective for telangiectasia, erythema, and rhinophyma and as such can be helpful for ETR and phymatous rosacea. Laser therapy emits light selectively absorbed by oxyhemoglobin and can destroy vessels selectively without damaging surrounding tissue. Standard pulsed dye and longer pulsed dye lasers are used for telangiectasia and erythema. Pulsed dye lasers at 577 nm, 585 nm, and 595 nm have been used to treat rosacea since the 80's. With a 585 nm pulsed dye laser, 5 to 7 mm spots and 0.45 millisecond pulses have been reported to be successful. Telangiectasia was reduced or eliminated in all rosacea patients in one or two treatments in one study. Two treatments 8 weeks apart with longer wavelength 595 nm laser with 1.5 millisecond pulse showed improvements in symptoms and Dermatology Quality of Life Index score, and erythema has measured by spectrophotometry.

Treatment of phymatous rosacea requires physical destruction of the nodularities. Topical and oral medications do not help other than reducing inflammation and as such patients may need more aggressive therapy. The best results are achieved using a CO2 laser which can be used in cutting mode to reduce the bulk of the nose. Tissue is vaporized and the shape of the nose can be remodeled.

Laser treatments are generally spaced four  weeks apart and  three or four treatments are needed. Vascular laser therapy  is not generally covered by insurance. Edema, pain, and bruising can occur with laser therapy.

Intense Pulsed Light therapy (IPL) uses multi-chromatic light at multiple wavelengths from yellow to infrared to penetrate the skin at vary depths.

A study of IPL in rosacea patients found improvements in flushing, reduced erythema, and fewer breakouts.  By targeting melanin and hemoglobin, IPL is effective for treating telangiectasias observed with ETR and PPR rosacea.  Because IPL therapy can target larger areas than lasers and long-term improvement in erythema has been demonstrated as well.

Intense pulsed light sessions are generally repeated every two to three weeks and patients may require four to six sessions. Treatments are generally not covered by insurance. Side effects are usually transient edema and erythema. Hypopigmentation is rare but can occur in darker skin types.

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The results of IPL or Laser are not permanent but can often give significant and long lasting improvement.  Patients often require one or two follow up treatments on an anual basis.

IPL or Laser is most helpful for rosacea when it is part of a complete program including a reduction in triggers for blushing, sun protection, treatment of inflammation and acne lesions with topical and sometimes oral antibiotics, as well as corrective camouflage, in some cases.

Skin Care and Camouflage Most rosacea patients report sensitive skin and are prone to irritation from products, so skin care is an essential part of preventing rosacea flares.

The recommended daily routine for rosacea patients is: 

• gentle facial cleanser
• broad spectrum sunscreen (minimum SPF 45)
• moisturizer

Tips for reducing skin irritation Cleansers need to be soap free (i.e. no alkaline agents.) Cetaphil was demonstrated to not induce irritation in rosacea patients. Patients are advised to avoid astringents, toners, products containing menthol, camphor, witch hazel, sodium lauryl sulfate, peppermint, salicylic acid, eucalyptus oil, or clove oil.

To minimize mechanical irritation, it is preferable to use fingers compared to pads or wash cloths for cleansing and applying products. Non-irritating moisturizer was demonstrated to improve patients' skin sensitivity as well as contribute to restoration of the skin barrier when used in conjunction with topical therapy. Protective moisturizer needs to be applied one to two times a day before other products.

Green tinted make-up can be applied under foundation to camouflage redness. Light foundations containing silicones that are easy to spread are recommended. Waterproof cosmetics and heavy foundations need to be avoided since heavy irritating cleansers are needed to remove them.

While these tips are starting places, patients will have to go through trial and error to find non-irritating products.

 Ocular rosacea management requires an analogous management strategy including:   

•  trigger reduction
• eye lid hygiene
• artifical tears
• oral Antibiotic therapy

Eye lid hygiene includes hot compresses applied to eyelid margins to liquefy the thick glandular secretions which cause styes. Commercially prepared eyelid scrubs or wipes may also be used.

Artificial tears with nonpreservatives are recommended to address eye dryness and itching.

Oral antibiotic therapy is necessary in patients who are symptomatic and or have progressing disease. Both tetracycline (1g/day) and doxycycline (100 mg/day) demonstrated effective treatment of ocular rosacea at 6 weeks and 3 months. Oral antibiotics are only needed when a patient has a flare or is symptomatic,  they do not need to be used in asymptomatic patients for ocular rosacea.
 

Summary and Conclusions
Rosacea is a chronic, relapsing skin condition with the greatest incidence in adults            aged  forty to seventy. Women have greater incidence, but men have greater severity.

Determining the subtype of rosacea is essential to identifying the best treatment plan.

Trigger reduction, antibiotic therapies (oral and topical), skincare, and laser and intense pulsed light therapies are the cornerstones of rosacea management.
 

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Pelle MT, Crawford GH, James WD. Rosacea: II. Therapy:499-512.
Wilkin J, Dahl M, Detmar M, et al. Standard grading system for rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Amer Acad Dermatol. 2004;51(3):907-912.
Van Zuuren EJ, Gupta AK, Gover MD, Graber M, Hollis S. Systematic review of rosacea treatments. J Amer Acad Dermatol. 2007;56(1);107-115.
Spadin AN, Flieshmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Amer Acad Dermatol. 2006;54(2):258-65. Butterwick KJ, Butterwick LS, Han A. Laser and light therapies for acne rosacea. J Drugs Dermatol. 2006;5(1):35-9.
Randleman B, Loft E, Song CD. eMedicine: Ocular Rosacea http://emedicine.medscape.com/article/1197341-overview