rosacea
ROSACEA
Rosacea is a chronic cutaneous disease of the convexities of the central face (cheeks, chin, nose and central forehead) w/ periorbital and perioral skin sparing. This condition is attributed to chronic vasodilation.
Remissions and exacerbations are common.
It typically appears after 30 years of age but may occur at any age.  It commonly affects fair-skinned individuals.
The common presenting symptoms are facial flushing, stinging/burning erythema, telangiectasia, edema, papules, pustules, ocular lesions, and hypertrophy of the sebaceous glands of the nose with fibrosis.
A history of episodic flushing often heralds onset of rosacea.

Principles of Therapy

  • 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 thru 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

Pharmacotherapy

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
    • Eyelid hygiene using application of warm compresses twice daily also helps improve symptoms
  • 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 first-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 first-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

Ciclosporin

  • Reserved for patients with moderate ocular features and must be prescribed by an ophthalmologist

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 first-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

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

Non-Pharmacological Therapy

Physical Modalities and Devices

Ablation Therapy

  • May be useful when telangiectatic component is prominent in moderate-severe erythematotelangiectatic rosacea
  • Indicated in patients with clinically noninflamed phyma
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Infectious Diseases - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
01 Dec 2019
Macrolide antibiotics are derived from the Streptomycesspecies. These contain either 14-membered (erythromycin [ERM],clarithromycin [CAM], roxithromycin [RXM]), 15-membered(azithromycin [AZM]) or 16-membered (spiramycin, josamycin,midecamycin) macrocyclic lactone rings. They inhibit proteinsynthesis by reversibly binding to the 23S ribosomal RNA (rRNA)in the 50s subunit of the bacterial ribosome. Traditionally,macrolides are used as first-line agents in respiratory, skin,soft tissue, and urogenital infections, and they are also activeagainst gram-positive cocci and atypical pathogens.