Acne Rosacea

Rosacea is a chronic inflammatory skin disease of the central face, characterised by persistent erythema, flushing, telangiectasia, inflammatory papules and pustules, and, in some patients, phymatous change and ocular involvement. It affects an estimated 5% of adults worldwide, most commonly fair skinned people aged 30 to 60 years (the Celtic phenotype), though it occurs in all skin types and is underdiagnosed in darker skin. Women are affected more frequently, but men tend to have more severe disease and phymatous change (rhinophyma).

Pathogenesis combines dysregulated innate immunity (overexpression of cathelicidin and kallikrein-5, producing the pro inflammatory peptide LL-37), neurovascular dysregulation (TRPV1 and TRPA1 channels, vasodilation), Demodex folliculorum mite proliferation and Bacillus oleronius antigens, ultraviolet damage, and genetic predisposition. Small intestinal bacterial overgrowth and Helicobacter pylori have been associated but are not established as causes.

Rosacea is now diagnosed by phenotype rather than the older fixed subtypes:

• Diagnostic phenotypes: fixed centrofacial erythema in a characteristic pattern that may periodically intensify, and phymatous changes
• Major phenotypes: flushing (transient erythema), papules and pustules, telangiectasia, and ocular manifestations (lid margin telangiectasia, blepharitis, conjunctivitis, keratitis, and chalazia)
• Secondary features: burning and stinging, oedema, dryness, and ocular symptoms

The older four subtypes remain in use clinically: erythematotelangiectatic (subtype 1), papulopustular (subtype 2), phymatous (subtype 3) and ocular (subtype 4).

Triggers include sun exposure, heat and hot beverages, alcohol (especially red wine), spicy foods, emotional stress, strenuous exercise, cold wind, hot baths, topical irritants, and some medicines (vasodilators, topical steroids, niacin).

• Transient flushing episodes lasting minutes, triggered by the factors above, often with burning or stinging

• Persistent erythema of the central face (cheeks, nose, forehead, chin), with spared periocular areas

• Visible telangiectasias

• Papules and pustules without comedones (the main distinction from acne vulgaris), which can be accompanied by swelling and a rough texture

• Phymatous changes: sebaceous hyperplasia and fibrosis with a bulbous nose (rhinophyma, commonest in men), also affecting the chin (gnathophyma), forehead (metophyma), ears (otophyma) and eyelids (blepharophyma)

• Ocular rosacea (in up to 50 to 60% of patients; may precede skin disease in about 20%): dry eye symptoms, grittiness, burning, photophobia, blepharitis, meibomian gland dysfunction, recurrent chalazia and styes, conjunctival injection, and, in severe cases, keratitis, corneal ulceration, and vision loss

• Rare variants: granulomatous rosacea (monomorphic firm yellow brown or red papules), rosacea fulminans (pyoderma faciale; sudden severe pustular and nodular disease in young women), and steroid induced rosacea after topical corticosteroids

Diagnosis is clinical, based on history and morphology. Investigations are used when the diagnosis is uncertain:

• Skin scraping or standardised skin surface biopsy for Demodex density (more than 5 mites per cm squared suggests a role)
• Biopsy for granulomatous variants or to exclude lupus, sarcoidosis and other granulomatous disease
• ANA and dermatological review if lupus is suspected
• 24-hour urinary 5-hydroxyindoleacetic acid or serum chromogranin A if carcinoid is suspected with flushing, diarrhoea and wheeze
• Ophthalmology assessment for any ocular symptoms, including slit lamp examination
• Review of medications and topical steroid history

General measures. Identify and avoid triggers (a trigger diary helps), daily broad spectrum sunscreen SPF 30 or higher (mineral filters tolerate better), gentle non-soap cleansers, fragrance free moisturisers, avoid astringents and scrubs, and camouflage with green tinted concealers.

Stop any topical corticosteroid (it can cause rebound flare; taper slowly if used for a long time).

Persistent erythema.

• Brimonidine 0.33% gel, once daily (alpha-2 agonist, vasoconstriction in about 30 minutes, effect up to 12 hours; risk of rebound erythema)

• Oxymetazoline 1% cream once daily (alpha-1 agonist, fewer rebound reports but may occur)

• Pulsed dye laser or intense pulsed light for persistent erythema and telangiectasia (typically 1 to 3 sessions, 4 to 6 weeks apart)

• Flushing: carvedilol 3.125 to 6.25 mg twice daily (off label), clonidine 0.05 mg twice daily, or propranolol 10 to 20 mg as needed

Papules and pustules (mild to moderate).

• Ivermectin 1% cream once daily for up to 12 weeks (effective and well tolerated, with antiparasitic and anti-inflammatory effects)

• Azelaic acid 15% gel or foam twice daily (can sting initially)

• Metronidazole 0.75% cream or gel twice daily or 1% once daily

• Topical minocycline 1.5% foam, and sulfacetamide sulfur preparations as alternatives

Moderate to severe papulopustular rosacea.

• Doxycycline 40 mg modified release capsule (30 mg immediate and 10 mg delayed release) once daily for 12 to 16 weeks; works through anti-inflammatory rather than antibacterial effects, so avoids resistance. Standard doxycycline 50 to 100 mg daily or twice daily is also used. Alternatives: minocycline 50 to 100 mg daily, azithromycin 250 mg three times a week, clarithromycin 250 to 500 mg twice daily

• Combine oral and topical therapy for faster response, and maintain with topical therapy after systemic treatment is stopped

• Isotretinoin 0.25 to 0.3 mg/kg/day for 12 to 20 weeks in refractory cases, rosacea fulminans (with prednisolone 0.5 to 1 mg/kg/day initially) and phymatous disease, with standard isotretinoin precautions (pregnancy prevention, liver and lipid monitoring)

• Metronidazole oral 200 to 250 mg twice daily is an alternative if tetracyclines are contraindicated, such as in pregnancy (erythromycin 250 to 500 mg twice daily is safer in pregnancy)

Phymatous rosacea. Early inflammatory disease responds to isotretinoin. Established rhinophyma needs surgical correction: CO2 laser ablation, electrosurgery, cryosurgery, dermabrasion, or tangential excision, with generally good cosmetic results and a low scarring risk.

Ocular rosacea. Eyelid hygiene (warm compresses for 5 to 10 minutes then gentle lid scrubs twice daily), preservative free artificial tears, topical azithromycin 1% eye drops, oral doxycycline 40 to 100 mg daily or azithromycin, topical cyclosporine 0.05% twice daily, and short courses of topical steroids under ophthalmic supervision for keratitis. Meibomian gland expression, intense pulsed light for evaporative dry eye. Urgent ophthalmology review for corneal involvement.

Review. Assess at 4 to 8 weeks, then every 3 to 6 months. Rosacea relapses are common, and long term maintenance with topical agents (ivermectin, azelaic acid or metronidazole) reduces recurrence. Provide psychological support for patients with social anxiety, which is common.