What are the best treatment options for rosacea?

Rosacea Etiology and Treatment

Etiology of Rosacea

The pathophysiology of rosacea involves a complex interplay of genetic predisposition, neurovascular dysregulation, innate immune system dysfunction, and environmental triggers, though the exact etiology remains incompletely understood. 1

Key pathophysiologic mechanisms include:

• Genetic susceptibility combined with intrinsic and extrinsic factors that influence phenotypic expression 1
• Neurovascular dysregulation leading to persistent and transient erythema 2
• Innate immune dysfunction contributing to inflammatory papules and pustules 3
• Demodex folliculorum infestation may play a role when concentrations exceed 5/cm² 4

Treatment Approach: Phenotype-Based Strategy

Modern rosacea management requires a phenotype-based approach targeting specific clinical features rather than traditional subtype classification, as this better addresses the spectrum of presentations and allows simultaneous treatment of multiple features. 2

First-Line Topical Treatments for Inflammatory Papules/Pustules

For mild papulopustular rosacea, initiate topical ivermectin 1% cream or azelaic acid 15% gel/foam as first-line monotherapy. 2, 3

• Topical ivermectin 1% cream demonstrates superior efficacy compared to metronidazole (83% vs 73.7% lesion reduction at 16 weeks) 3
• Azelaic acid 15% gel/foam serves as an equally effective alternative first-line option 2
• Encapsulated benzoyl peroxide 5% (E-BPO 5%) is FDA-approved with the most rapid onset (significant improvement by week 2) and sustained efficacy through 52 weeks 2, 3
• Topical minocycline foam 1.5% is recommended for moderate to severe inflammatory lesions 2
• Topical metronidazole remains an option but is less effective than ivermectin 3, 5

Treatment for Moderate-to-Severe Papulopustular Rosacea

For moderate-to-severe disease, use combination therapy with oral doxycycline 40 mg modified-release plus a topical agent (ivermectin or azelaic acid). 3

• Doxycycline 40 mg modified-release provides anti-inflammatory activity without antibiotic effects, reducing gastrointestinal side effects and antibiotic resistance concerns 2, 3
• This formulation can be used across all severities including ocular rosacea 2
• Combination therapy (topical plus systemic or multiple topicals) is typically required for moderate and severe presentations 2

Treatment for Persistent Erythema

For persistent erythema, use topical brimonidine or oxymetazoline as first-line therapy. 2

• Topical brimonidine (α-adrenergic) is the primary recommendation 2, 5
• Topical oxymetazoline serves as an alternative 2
• Warning: Both vasoactive agents can cause rebound erythema with continuous use 2
• Oral beta blockers (carvedilol) may be considered for persistent erythema, though evidence is limited 2

Treatment for Transient Erythema/Flushing and Telangiectasia

For severe transient erythema/flushing, use pulsed-dye laser (PDL) or intense pulsed light (IPL) as physical modalities are the primary treatment. 2

• For telangiectasia: Electrodessication, IPL, or PDL are the treatments of choice 2
• Topical α-adrenergics or oral beta blockers may provide adjunctive benefit 2

Treatment for Phymatous Changes

For clinically inflamed phymatous changes, use oral doxycycline 40 mg modified-release; for noninflamed cases, use electrodessication, IPL, or lasers. 2

• Severe phymatous changes may require procedural interventions including electrosurgery, dermabrasion, or surgical resurfacing 6

Ocular Rosacea Management

For mild ocular symptoms, initiate eyelid hygiene and artificial tears immediately; for moderate-to-severe ocular rosacea, use oral doxycycline as first-line pharmacological treatment. 2, 7

Mild Ocular Rosacea

• Eyelid hygiene combined with artificial tear substitutes for mild burning/stinging 7
• If symptoms don't respond within 2-4 weeks, refer to ophthalmology 7

Moderate-to-Severe Ocular Rosacea

• Oral doxycycline (standard formulations ≥50 mg or 40 mg modified-release) for 6-12 weeks minimum 2, 7
• Combination therapy with lid hygiene, artificial tears, and oral doxycycline achieves 90% response rate 7
• Topical cyclosporine 0.05% may help with posterior blepharitis 7
• Brief topical corticosteroids for severe inflammation, then taper; avoid long-term use due to glaucoma and cataract risk 7

When to Refer to Ophthalmology

Refer for: 7

• Any symptoms beyond mild burning/stinging
• Symptoms not controlled with lid hygiene alone
• Blurred vision, photophobia, or foreign body sensation
• Recurrent chalazia or hordeola
• Any corneal involvement
• All pediatric patients with ocular symptoms

Treatment Duration and Failure Management

Allow 6-8 weeks for topical agents and 8-12 weeks for oral agents before declaring treatment failure. 2

• If first-line treatment fails: Switch to an alternative first-line topical agent or add oral doxycycline 40 mg 3
• For severe refractory disease: Consider oral isotretinoin 3
• Very low-dose isotretinoin demonstrates 91% clearance or excellent response in mild to moderate papulopustular rosacea 2

Maintenance Therapy

Without maintenance therapy, up to two-thirds of patients relapse when treatment is discontinued; continue the minimum treatment necessary to maintain remission. 2, 3

• Topical agents alone may suffice for maintenance after initial combination therapy 3
• Long-term doxycycline 40 mg has demonstrated safety for extended use 3
• The approach depends on treatment modality, patient preference, and initial severity 7

Essential Adjunctive Measures for All Patients

All patients require general skincare including daily sun protection with SPF 30+, gentle non-medicated cleansers, moisturizers to support skin barrier function, and trigger avoidance. 2, 3

• Sun protection (SPF 30+) daily 2, 3
• Gentle cleansers and moisturizers 2
• Trigger avoidance: Spicy foods, alcohol, extreme temperatures (though RCT evidence is limited) 2, 3

Critical Pitfalls to Avoid

• Don't treat based on traditional subtypes—use phenotype-based approach targeting specific presenting features 3
• Don't use traditional non-encapsulated benzoyl peroxide—only E-BPO 5% is FDA-approved for rosacea with reduced irritation 3
• Don't discontinue treatment prematurely—this leads to false treatment failures 3
• Don't extrapolate acne treatment protocols to rosacea—fundamentally different pathophysiology 2
• Don't overlook ocular manifestations—leads to underdiagnosis and undertreatment 2
• Don't use tetracyclines in pregnancy, nursing women, or children under 8 years—absolute contraindication 3, 7
• Counsel patients about photosensitivity with doxycycline 3