Rosacea Treatment

• Rosacea is a chronic disease with relapses; therefore, long-term treatment is usually required
  
  • Treatment should start early to prevent progression of the disease to the stages of edema and irreversible fibrosis
• Best approach to management of rosacea is through assessment of the spectrum of clinical features/phenotypes present in each patient
• Phenotype-based management requires parallel combination therapy
• No single therapy completely addresses all rosacea features; multiple treatment modalities either in combination or staggered in their sequence of use is needed to address the spectrum of features in each patient
  • Pharmacological therapy used in combination with physical devices have better outcomes than either treatment modality used alone
• Choice of combination of treatment modalities is based on disease activity, severity and presenting features, and taking into consideration the patient's desire for treatment
• Sufficient time for each treatment modality to take effect should be allowed before considering treatment failure and choosing another modality
  • Duration of initial treatment may vary from 6-12 weeks depending on whether topical or oral agents are used and must be tailored to the patient
• Avoid long-term use of antibiotics
  • Slowly reduce the dose of oral antibiotics after 6-12 weeks then switch to topical agents
• Maintenance therapy is needed due to the chronic nature of the disease and because there is no definite cure to the disorder
  • Long-term topical treatment is primarily recommended and subantimicrobial doses of Doxycycline are an option for those intolerant or unresponsive to topical agents

Goals of Treatment

• Achieving clear/almost clear skin
• Reduction in severity of manifestations
• Reduction in frequency of flares
• Improvement in patient-reported features
• Reduction in the impact on the quality of life of the patient
• Patient satisfaction with treatment

Symptom Recurrence

• If recurrence is infrequent, treatment course can be repeated
• If frequent, patient can be maintained on a lower dose of the antibiotic used in the previous treatment regimen that improved the symptoms

Topical Therapy

• Topical agents should be used for at least 6-8 weeks for accurate assessment of therapeutic response
• Maintenance therapy with topical agents of up to 6 months is recommended to sustain control of papulopustular lesions

Alpha-adrenergic Receptor Agonists

• Brimonidine
  • An alpha₂-adrenergic agonist that reduces facial erythema through direct cutaneous vasoconstriction
  • Recommended for the treatment of persistent facial erythema

• Oxymetazoline
  • A selective alpha₁-adrenergic receptor agonist indicated for the treatment of persistent facial erythema

Antibiotics

• Topical treatment is frequently used for mild symptoms and maintenance of remission after discontinuance of systemic therapy
• Topical maintenance therapy for 6 months is generally advised
• Topical application should be across the entire face rather than only on the lesions
• For mild ocular rosacea, topical antibiotics are used together with artificial tears
  
  • May help soften any collarettes and allow easy removal during eyelash hygiene 
  • Topical Azithromycin is as effective as oral Doxycycline in treating ocular rosacea with lesser adverse effects as demonstrated by recent studies

• Erythromycin and Clindamycin
  • These agents combined with Benzoyl peroxide have been shown in two different randomized controlled trials (RCTs) to be effective for inflammatory rosacea; adverse reactions include burning sensation and itching at site of treatment
  • Used as an alternative in patients with mild-moderate inflammatory papules/pustules and intolerant or unresponsive to Azelaic acid, Ivermectin or Metronidazole
  • May also be used as monotherapy in patients with inflammatory papules/pustules

• Ivermectin
  • A synthetic derivative of avermectins that is used for the treatment of inflammatory lesions, bumps or pimples of rosacea produced by Streptomyces avermitilis
  • Exerts anti-inflammatory effects by inhibiting lipopolysaccharide-induced production of inflammatory cytokines
  • Recommended as one of the 1st-line therapies for all severities of inflammatory papules/pustules
  • Treatment of choice over Azelaic acid for patients with significant facial sensitivity
  • An RCT has shown Ivermectin to be more effective in reducing inflammatory lesions and produce longer remissions after treatment compared with Metronidazole
  • Treatment is well tolerated and safety and effectivity with long-term treatment of up to 52 weeks is known

• Metronidazole
  
  • Most effective treatment for inflammatory papules/pustules and helps in the improvement of facial erythema
    • Generally well tolerated with few local adverse reactions to skin (eg burning and stinging sensation)
  • Has antimicrobial, anti-inflammatory and antioxidant properties believed to be involved in the improvement of symptoms of rosacea 
  • May be initiated at the same time as oral antibiotic and continued after discontinuation of oral drug
    
    • May be used as indefinite maintenance therapy after clearance with oral treatment
    • Helps to prevent relapse

• Sulfacetamide/Sulfur
  
  • Used as an alternative in patients with mild-moderate inflammatory papules/pustules and intolerant or unresponsive to Azelaic acid, Ivermectin or Metronidazole
  • Sulfacetamide has antibacterial and anti-inflammatory action while Sulfur has antidemodectic, antifungal and keratolytic effects

Azelaic Acid

• Naturally occurring dicarboxylic acid with antibacterial, anti-inflammatory, antioxidative and antikeratinizing activities 
• Recommended as one of the 1st-line agents for the treatment of mild-moderate inflammatory papules/pustules
  • Not effective for telangiectasia
• Two double-blind RCTs concluded that Azelaic acid is comparable to or exceeds Metronidazole in clinical effectiveness in treating erythema, nodules, papules and pustules
• Adverse reactions were insignificant and short-lived

Calcineurin Inhibitors

• Eg Ciclosporin, Tacrolimus 
• Reserved for patients with moderate ocular features and must be prescribed by an ophthalmologist
• Ciclosporin may be used for 2-3 months; topical steroid rosacea-like reaction may develop from long-term use 
• Tacrolimus is applied on the lashes and pulsed 1-2 weeks/month for 3-6 months

Permethrin

• May be used as an alternative to patients with inflammatory papules and pustules and intolerant or unresponsive to Azelaic acid, Ivermectin or Metronidazole
• An RCT has shown improvement in patients with inflammatory papules/pustules equivalent to Metronidazole and superior to placebo
• More studies are needed as safety of long-term Permethrin treatment is unknown

Retinoids

• Useful for actinically damaged skin which is common in rosacea
  
  • Has beneficial effect on vascular component of the disease (eg flushing, redness, and thread veins)
• Used as an alternative agent in patients with mild-moderate inflammatory papules/pustules and intolerant or unresponsive to Azelaic Acid, Ivermectin or Metronidazole
• Has anti-inflammatory and extracellular repair matrix properties
• Adverse reactions and slow onset of effect tend to limit use; however, better tolerated agents (eg Adapalene) may be considered

Oral Therapy

Antibiotics

• Indicated for moderate-severe papulopustular rosacea and when topical therapy failed
  • Also indicated for ocular manifestations of rosacea

• A number of agents can be used:
  
  • Tetracycline and its derivatives (eg Doxycycline, Lymecycline, Minocycline, and Oxytetracycline), macrolides (eg Azithromycin, Clarithromycin and Erythromycin) and Metronidazole are commonly used
  • Tetracyclines, specifically oral Doxycylcine, are indicated as 1st-line agents for all severities of ocular features, clinically inflamed phyma and inflammatory papules/pustules secondary to rosacea
  • Two RCTs have shown subantimicrobial dose of Doxycycline, alone or with topical Metronidazole, reduces inflammatory lesions in moderate-severe rosacea
    • Subantimicrobial dose of Doxycycline is the choice for long-term oral treatment in patients who fail to maintain improvement or are intolerant to topical therapy
  • Macrolides are used in patients intolerant or unresponsive to tetracyclines

• It is continued until inflammatory lesions resolve or for 3 months, whichever comes first
• Since long-term use of antibiotics may lead to resistant bacterial strains, subantimicrobial dosing should be considered

Retinoid

• Low-dose Isotretinoin therapy has been used to treat refractory rosacea
• Used in patients with inflammatory papules and pustules who are unresponsive to topical agents and oral antibiotics
• Indicated also in patients with clinically inflamed phyma
• One small RCT reported that low-dose oral Isotretinoin reduced erythema, papules and telangiectasia by 9th week of treatment
  
  • In patients with rhinophyma, there was decrease in size and number of sebaceous glands with oral Isotretinoin
• Adverse effects and teratogenicity may limit use
  • Avoid in patients with significant ocular symptoms as this can lead to worsening of symptoms and severe keratitis

Other Therapies

Benzoyl Peroxide

• Alternative for patients with inflammatory papules/pustules who are intolerant or unresponsive to Azelaic acid, Ivermectin or Metronidazole

Clonidine

• Low dose may be effective in controlling flushing especially in postmenopausal women

Emollients

• May help soothe and repair damaged skin
• Various emollients, cleansers and skin protectives are available. Please see prescribing information for specific formulations in the latest MIMS

Nonselective Beta-blockers 

• Eg Carvedilol, Nadolol, Propranolol
• May be used to relieve erythema and flushing
• Mechanism of action is through inhibition of beta-adrenergic receptors on the smooth muscles of surrounding blood vessels leading to vasoconstriction
• Used at low dose to avoid adverse effects

Topical Steroids

• Indicated for severe ocular rosacea (sclerokeratitis) 
• May be used short term for severe inflammation
• Potential for exacerbation and long-term side effects limit its use

Ablation Therapy

• May be useful when telangiectatic component is prominent in moderate-severe erythematotelangiectatic rosacea
• Indicated in patients with clinically noninflamed phyma