Rosacea

Background

• Affects approximately 5% of adults worldwide
• Chronic, common cutaneous condition
• Characterized by facial flushing and a variety of clinical signs
• Four primary subtypes:
  • erythrotelangiectatic
  • inflammatory
  • phymatous
  • ocular
• Different subtypes require different therapies
• Affects self-esteem significantly
• Under-recognized in patients with skin of color
• Associated with:
  • Depression
  • Hypertension
  • Cardiovascular diseases
  • Anxiety disorder
  • Dyslipidemia
  • Diabetes mellitus
  • Migraine
  • Rheumatoid arthritis
  • Helicobacter pylori infection
  • Ulcerative colitis
  • Dementia

Clinical Features

• Primary feature: Persistent erythema in the central face for at least three months
• Other findings: flushing, telangiectasia, edema, inflammatory papules, pustules, ocular symptoms, rhinophyma

Demographics

• Most common in fair-skinned individuals of European or Celtic origin
• Affects individuals of any ethnic group
• Equal gender distribution, despite previous thoughts that it affects women more
• Can occur at any age, occasionally in children
• Peaks at ages 30-50 years
• Incidence: 10% in Sweden, 0.09% to 22% in the UK

Pathophysiology

• Genetic vascular reactivity:
  • Genetic component, higher in Celtic or northern European descent
  • Increased blood vessel density near skin surface
  • Triggered by harsh climate, extreme temperatures, solar radiation, emotion, spicy food, alcohol, hot beverages
• Demodex mites:
  • Association with Demodex follicularum
  • Mites live in sebaceous follicles
  • Stimulate mononuclear cells, causing inflammation
  • Treatment with topical ivermectin improves inflammatory rosacea
• Cathelicidin:
  • Elevated epidermal serine protease activity in rosacea patients
  • Causes deposition of pro-inflammatory cathelicidin-derived peptides
  • Normalizes when skin barrier is restored

Subtypes and Clinical Manifestations

Cutaneous Features:

• Transient recurrent erythema (flushing)
• Persistent facial erythema
• Telangiectasia
• Facial skin and eyelid margin telangiectasia
• Often termed erythematotelangiectatic rosacea
• Inflammatory papules and pustules (papulopustular)
• Phymatous changes (thickening of the skin due to hyperplasia/fibrosis of sebaceous glands)
  • Most commonly affects the nose (rhinophyma)
  • More common in men

• Erythrotelangiectatic (ETR; vascular):
  • Characterized by flushing and vasodilation
  • Leads to permanent erythema and telangiectasia
  • Affects central face, sometimes ears, neck, or upper chest
  • Common triggers: harsh climate, extreme temperatures, solar radiation, emotion, spicy food, alcohol, hot beverages

• Papulopustular Rosacea (PPR)
  • Also known as inflammatory rosacea
  • Characterized by persistent or episodic development of inflammatory papules and pustules
  • Often affects the central face
  • May have background erythrotelangiectatic rosacea (ETR)
  • Common in middle-aged women

• Phymatous Rosacea
  • Characterized by hyperplasia of skin due to chronic inflammation
  • Most commonly affects the nose, leading to rhinophyma
  • Occurs mostly in older men
  • Often presents with significant telangiectasia over affected regions

• Ocular Rosacea
  • Ocular manifestations can precede or occur concurrently with cutaneous signs
  • Primarily affects adults, occasionally children
  • Affects males and females equally
  • Common findings: blepharitis and conjunctivitis
  • Severe cases may require assessment by an ophthalmologist

Differential Diagnosis

• Seborrhoeic Dermatitis:
  • Scaling and erythema on eyebrows, nasolabial folds, scalp, and pre-sternal areas
  • Can coexist with rosacea (seborosacea)
• Periorofacial Dermatitis:
  • Inflammatory papules around mouth, eyes, and nasal area
  • Often caused by prolonged use of potent topical corticosteroids
• Acne Vulgaris:
  • Comedonal lesions, papules, pustules, cysts
  • Commonly affects face, back, and chest
  • Patients may experience both rosacea and acne
• Keratosis Pilaris:
  • Fixed blush appearance on lateral cheeks with fine follicular keratotic plugs
  • Autosomal dominant inheritance
  • Also affects posterior arms and anterior thighs
• Systemic Lupus Erythematosus (SLE):
  • Malar erythema, photosensitivity, pigment change, follicular plugging, scarring
  • Presence of systemic disease favors SLE diagnosis

Complications

• Phymatous rosacea
• Inflammatory eye complications, eg, blepharokeratoconjunctivitis, sclerokeratitis
• Physical discomfort, eg, from ocular symptoms
• Negative psychosocial effects such as increased anxiety, depression, low self-esteem, and social isolation
• Trigger avoidance leading to lifestyle limitatio

Diagnostic criteria

• Persistent centrofacial erythema associated with periodic intensification by potential trigger factors
• Phymatous changes.

Major criteria (must occur in centrofacial distribution)

• Flushing/transient centrofacial erythema
• Inflammatory papules and pustules
• Telangiectasia — visible blood vessels (excluding nasal alar telangiectases, which are common in adults)
• Ocular rosacea (lid margin telangiectasia, blepharitis, keratitis/conjunctivitis/sclerokeratitis/anterior uveitis).

Minor features

• Burning sensation of the skin
• Stinging sensation of the skin
• Oedema
• Dry sensation of the skin.

In cases where there is diagnostic uncertainty, skin biopsy may be considered.

Treatment

• General Measures:
  • Avoid triggers
    • Emotional stress
    • Hot or cold weather
    • Sun exposure
    • Wind
    • Exercise
    • Hot drinks
    • Alcohol consumption
    • Spicy foods
    • Dairy products
    • Hot baths or showers
    • Certain skin care products
    • Certain cosmetics
    • Medications (eg topical steroids, niacin, beta blockers)
• General Measures
  • Inform patient of chronic, intermittent and inflammatory nature of rosacea
  • Encourage patient to keep a journal documenting exposures, diet and activities that cause flare-ups
  • Daily use of broad-spectrum sunscreen, avoidance of midday sun, shade, protective clothing
  • Soap-free and abrasive-free cleansers
  • Moisturisers should be used if the skin is dry
  • Avoid use of abrasive materials and pat dry for better absorption of moisturisers
  • Cosmetics with green or yellow tint applied to the central face may conceal redness
  • Topical corticosteroids are relatively contraindicated on the face

Systemic Treatment

• Avoid use of topical steroids as they may aggravate the condition
• Oral Antibiotics:
  • Doxycycline: 50 to 100 mg orally, once daily until a response is seen (usually 3 to 4 weeks, up to 8 weeks). – eTG
  • Erythromycin: 250 to 500 mg orally, twice daily until a response is seen (usually 3 to 4 weeks, up to 8 weeks).– eTG
  • Erythromycin ethyl succinate: 400 to 800 mg orally, twice daily until a response is seen (usually 3 to 4 weeks, up to 8 weeks).– eTG
  • If not tolerated or inadequate response: Minocycline 50 to 100 mg orally, once daily until a response is seen (up to 8 weeks).– eTG
  • Other options: minocycline, erythromycin, cotrimoxazole, metronidazole
  • Anti-inflammatory effects reduce papules, pustules, ocular symptoms
• Isotretinoin:
  • For refractory papulopustular and phymatous rosacea
  • Dosage: 10–20 mg/day for 4-6 months
  • Prevents progression of rhinophyma

Maintenance Therapy (if rosacea recurs within a month):

• Doxycycline: 50 mg orally, once daily or every second day for 6 to 12 months.– eTG
• Minocycline: 50 mg orally, once daily or every second day for 6 to 12 months.– eTG
• If ineffective: Refer for dermatologist advice; low dose oral isotretinoin may be considered.– eTG

Topical Treatment

Apply for 6 to 12 weeks for maximal response. Recurrent intermittent therapy may be required.

• Metronidazole and Azelaic Acid:
  • First-line therapy for mild-to-moderate rosacea
  • Metronidazole 0.75% gel or cream: Apply once or twice daily. – eTG
  • Reduces oxidative stress and inflammatory lesions
• Ivermectin:
  • Ivermectin 1% cream: Apply once daily– eTG
  • Controls Demodex mites, effective in randomized controlled trials
• Azelaic acid:
  • Azelaic acid 15% gel: Apply once or twice daily– eTG
  • Azelaic acid 20% lotion: Apply once or twice daily– eTG

Central facial erythema without papulopustular lesions		Central facial erythema with papulopustular lesions		Phymatous
		Mild-to-moderate	Moderate-to-severe
General measures	Begin with a mild non-alkaline skin cleansing and moisturising routine Avoid abrasives and fragrances (eg alcohol, acetone) Use broad-spectrum sunscreen, SFP 30 or greater Educate on trigger avoidance	Begin with a mild non-alkaline skin cleansing and moisturising routine Avoid abrasives and fragrances (eg alcohol, acetone) Use broad-spectrum sunscreen, SFP 30 or greater Educate on trigger avoidance	Same as mild-to-moderate	Trigger avoidance Photoprotection
First-line therapy	Topical metronidazole (eg Flagyl, Metrogel) for inflammatory lesions or brimonidine (eg Mirvaso) for erythema Azelaic acid also advised as an alternative for inflammation	Topical metronidazole for inflammatory lesions Topical brimonidine for erythema if needed as adjunctive therapy Topical ivermectin for inflammation; may be used in combination with metronidazole	Topical metronidazole for inflammation plus anti‑inflammatory dose of doxycycline (50–100 mg daily) Topical brimonidine for erythema if needed as adjunctive therapy	Mid-to-high dose isotretinoin for 12–28 weeksMicrodose therapy for maintenanceTopical and/or oral antimicrobials as needed for inflammatory lesions
Second-line therapy	Vascular laser therapy (eg pulsed dye laser, intense pulsed light) for erythema and telangiectasia	Sub-antimicrobial (anti‑inflammatory) dose doxycycline (50–100 mg daily) Vascular laser therapy for erythema and telangiectasia	If limited or no response at 8–12 weeks, consider antimicrobial dose of doxycycline (100–200 mg daily) Vascular laser therapy for erythema and telangiectasia	Vascular laser therapy
Third-line therapy		If limited or no response at 8–12 weeks, consider antimicrobial (antibiotic) dose of doxycycline (100–200 mg daily)	If limited or no response, consider alternative oral antibiotic (eg metronidazole, azithromycin)	Ablative laser treatment, dermabrasion, surgical debulking
Refractory		Systemic isotretinoin Consider treatment in the moderate-to-severe category	If refractory to treatment consider oral isotretinoin

Vascular Laser Therapy and Intense Pulsed Light (IPL)

• Targets hemoglobin in vessels, effective for facial erythema and telangiectasia
• IPL also effective for rosacea
• Adverse effects: blistering, purpura, loss of pigmentation, ulceration, scarring

Specific Measures

Specific Measures for Transient erythema (flushing)

• Alpha-adrenergic agonists (topical brimonidine, topical oxymetazoline) — they are often used infrequently for special occasions only, as persistent use may result in rebound flushing on discontinuation
• Oral beta-blockers (carvedilol)
• Oral clonidine may reduce flushing

Specific Measures for Persistent erythema

• Alpha-adrenergic agonists (topical brimonidine, topical oxymetazoline, as above)
• Intense pulsed light therapy
• Vascular laser

Specific Measures for Phymatous Rosacea

• Early Disease:
  • Oral isotretinoin to reduce nasal volume
• Advanced Disease:
  • Mechanical dermabrasion, ablative laser resurfacing, surgical shave techniques for cosmetic improvement of rhinophyma

Specific Measures for Ocular rosacea

• General management
  • Increase dietary intake of omega-3 fatty acids
  • Warm compresses
  • Gentle eyelash/eyelid cleansing to express sebum trapped in the meibomian glands
• First-line medical management
  • If mild-moderate: topical azithromycin/topical calcineurin inhibitors
  • If severe: azithromycin, doxycycline.