Acne Rosacea

Epidemiology

Typical onset ages 30 to 50 years old
Northern european descent and fair skinned persons (esp. Fitzpatrick Skin Types 1 to 3)
More common in women by factor of 2-3
Prevalence
1. United States: 1.3-2.1% (14 Million cases)
2. Worldwide: Up to 5%

Risk Factors
Predisposing triggers and exacerbating factors

Nose Hair Follicle mites (Demodex folliculorum)
1. May predispose to inflammation and alter the skin microbiome
Triggers
1. Sun Exposure, hot weather, and hot baths
2. Emotional stressors
3. Alcohol use (esp. white wine, liquor; RR 4 for phymatous changes)
4. Hot drinks and spicy food
5. Exercise
6. May also be triggered by wind and Cold Weather

Pathophysiology

Acneiform eruption
Exaggerated inflammatory, immune and vascular response to triggers
Nose Hair Follicle mites (Demodex folliculorum) appear to be involved in pathogenesis

Types

Subtype 1: Erythematotelangiectatic (most difficult to treat)
1. Persistent central face Macular erythema with Telangiectasias and Flushing
2. Possible ocular involvement
Subtype 2: Papulopustular (easiest to treat)
1. Persistent central face erythema with small Papules and tiny Pustules (acne-like)
2. Periocular sparing
Subtype 3: Phymatous (more common in men)
1. Skin thickening and nodular irregularities (due to Sebaceous Gland hyperplasia)
2. Distribution: Nose (Rhinophyma), chin, ears, forehead or Eyelid
Subtype 4: Ocular
1. Watery, Bloodshot Eyes may become dry with foreign body Sensation and photophobia
2. Distribution: Blepharitis, Conjunctivitis, and Eyelid Inflammation
Variant: Granulomatous
1. Brown, yellow or red firm, indurated non-inflammatory Papules or Nodules

Symptoms

Stinging or burning pain may accompany facial Flushing
Flushing and swelling may be present
Eyes and skin may feel dry

Signs
Skin

Course is variable
1. Stages listed below are for organization only
Distribution for all lesions
1. Affects middle third of face (forehead to chin)
Findings in Skin of Color
1. Facial stinging, burning, dryness
2. Subjective facial Flushing
3. Postinflammatory Hyperpigmentation
Stage 1: Initial presentation
1. Intermittent facial Flushing lasting 5 minutes or less
2. May involve neck and chest
3. Sensation of warmth may be present
Stage 2: Early vascular changes
1. Facial erythema
  1. More evident in patient photographs when against a blue background
2. Telangiectasis
  1. Telangiectasias are more evident under Diascopy (blanched skin under a glass slide) or Dermatoscopy
3. Eye changes (see ocular signs below)
Stage 3: Inflammatory changes
1. Papules
2. Sterile Pustules
3. Comedones are typically absent
Stage 4: Rhinophyma (Red bulbous nose)
1. More common in men
2. Thickening of facial skin (especially nose)
  1. Connective tissue hypertrophy
  2. Sebaceous Gland hypertrophy
3. Previously thought to be a sign Alcohol Abuse
  1. Example: W. C. Fields
Variant: Granulomatous Rosacea
1. Facial Papules and Nodules with Granulomatous change
2. May appear similar to facial sarcoid

Signs
Ocular involvement (50% of Rosacea cases)

Eyelid Inflammation (may be presenting sign)
1. Acne involving Eyelids
2. Eyelid redness and swelling
3. Eyelid margin Telangiectasia
Inflammatory Conjunctivitis
1. Blepharitis may accompany Conjunctivitis (waxy, honey crust at lash bases)
2. Eyes that itch or burn
3. Dry Eyes with sandpaper or foreign body Sensation
Other less common changes
1. Corneal neovascularization
2. Keratitis
3. Anterior Uveitis
4. Corneal scarring (spade shaped Corneal infiltrates)

Differential Diagnosis
Skin

Late-onset Acne Vulgaris
1. Comedones present
2. No Telangiectasis
3. No eye symptoms or signs
Steroid-induced Acne
1. Results from Corticosteroid use on face (esp. perioral changes)
2. Systemic Corticosteroids may involve the entire face (unlike Rosacea which involves central face)
Perioral Dermatitis
1. Some dermatologists consider Perioral Dermatitis a variant of Rosacea
Systemic Lupus Erythematosus (SLE)
1. Malar Rash of SLE does not affect the nasolabial folds (unlike Rosacea)
Seborrheic Dermatitis
1. Seborrhea affects the hairline and scalp (unlike Rosacea)
Sarcoidosis
1. Facial sarcoid may appear similar to Granulomatous Rosacea
Polymorphous Light Eruption or other Photodermatitis
Contact Dermatitis
Atopic Dermatitis
1. Eczema or atopic history with skin dryness and Scaling
Dermatomyositis or Polymyositis
1. Periorbital violaceous (purple) dermatitis
Facial Infections
1. Gram Negative Folliculitis (complication of prolonged Antibiotic use in acne or Rosacea)
2. Tinea Barbae (beard area)
3. Tinea Faciei (sharply demarcated facial dermatitis)
Systemic conditions of Flushing
1. See Flushing
2. Carcinoid Syndrome (severe facial Flushing)
3. Mastocytosis
4. Pheochromocytoma

Differential Diagnosis
Ocular Rosacea

Blepharokeratoconjunctivitis (staphylococcal or seborrheic)
Sebaceous Gland carcinoma
Allergic Conjunctivitis

Diagnosis

See Types and signs as above
Central face dermatitis with at least one of the following findings
1. Transient erythema (Flushing)
2. Nontransient erythema
3. Papules and Pustules
4. Telangiectasia

Associated Conditions

Management
General Measures

General
1. Patients can identify their specific triggers in >90% of cases (log exposures and reactions)
2. Dietary changes alone can reduce Rosacea flares
Avoid triggers
1. Avoid Alcohol
2. Avoid prolonged heat exposure
3. Avoid hot liquids (coffee, tea)
4. Avoid heavy cosmetics
Use sun screen (minimum SPF 30) regularly (better tolerated agents are listed)
1. Avoid chemical Sunscreens which may be irritating
2. Use a mineral or physical Sunscreen
  1. Base: Simethicone, dimethicone or cyclomethicone
  2. Active ingredient: Titanium Dioxide or Zinc Oxide
Choose gentle skin care products
1. Clear and free (dye and perfume free) products
2. Mild cleansers with near neutral pH (e.g. cetaphil, dove sensitive skin) used twice daily
3. Skin Moisturizers (Emollients) applied to moist skin
4. Avoid abrasive skin products
5. Green or yellow tinted consmetics may hide facial erythema
Avoid provocative medications
1. Benzoyl Peroxide (avoid in erythematotelangiectatic Rosacea - subtype 1)
2. Topical Corticosteroids
No definitive evidence for dietary supplements
1. No significant benefit with Zinc or Vitamin D Supplementation
  1. Weiss (2017) Dermatol Pract Concept 7(4): 31-7 [PubMed]
2. Polyphenols may decrease Rosacea lesions
  1. Saric (2017) J Altern Complement Med 23(12): 920-9 +PMID: 28650692 [PubMed]

Management
Papular and Pustular Rosacea

Step 1
1. Apply across entire central face
2. First Line agents (most effective agents)
  1. Metronidazole topical
    1. Once daily (1% gel) or twice daily (0.75% gel, cream or lotion)
    2. Effective in 80% of cases
    3. Similar efficacy between 0.75% and 1%, as well as between once and twice daily dosing
  2. Azelaic Acid (Azelex) 15% gel
    1. Slight benefit over Metrogel, but less tolerated (consider in those not responding to Metronidazole)
    2. Gel is generic, while cream and foam are trade name only at twice the price
    3. Irritation may be reduced with gentle skin cleansers (e.g. cetaphil) and Skin Lubricants (e.g. vanicream)
    4. Avoid in Skin of Color (may alter pigmentation)
    5. Elewski (2003) Arch Dermatol 139:1444-50 [PubMed]
  3. Ivermectin (Scolantra) 1% cream (see below)
    1. Applied once daily
    2. May be more effective than Metronidazole, but is far more expensive
    3. Stein (2014) J Drugs Dermatol 13(3): 316-23 [PubMed]
3. Alternative agents that have been used historically in Rosacea
  1. Clindamycin (Cleocin-T)
  2. Sulfacetamide/Sulfur (10%/5%) cream, foam or lotion
  3. Permethrin 5% cream
    1. Effective for erythema and Papules (but not as effective with Pustules)
    2. Kocak (2002) Dermatology 205:265-70 [PubMed]
  4. Permethrin 2.5% with tea tree oil gel
    1. Reduces inflammation and decreases Demodex mite population
    2. Ebneyamin (2020) J Cosmet Dermatol 19(6):1426-31 +PMID: 31613050 [PubMed]
Step 2: May use the following oral agents in combination with topicals listed above
1. Doxycyline (preferred)
  1. Moderate Rosacea
    1. Doxycyline 40 mg daily or 20 mg twice daily (sub-antimicrobial dose)
    2. Lower dose has similar efficacy to the 100 mg dose
  2. Severe Rosacea or refractory to 8-12 weeks at lower dose Doxycycline
    1. Doxycycline 100 mg twice daily (then taper to once daily after the first month)
2. Alternative systemic Antibiotics (tapering to once daily after the first month)
  1. Tetracycline 250 mg twice daily or
  2. Erythromycin 250 mg twice daily
  3. Amoxicillin 250 mg twice daily
3. Efficacy
  1. Useful in treating Blepharitis, Keratitis
  2. Most effective treatment
Step 3: Additional topical agents to consider
1. Erythema (without Papules or Pustules)
  1. Brimonidine gel 0.33% (Mirvaso) - see below
  2. Oxymetazoline 1% (Rhofade) - see below
2. Inflammatory papular and pustular Rosacea
  1. Precaution: Avoid in erythematotelangiectatic Rosacea (Flushing) - subtype 1 (may worsen)
  2. Topical Benzoyl Peroxide with Clindamycin (e.g. Benzaclin)
    1. Avoid Benzyl Peroxide with Erythromycin (no benefit to the Erythromycin)
  3. Ivermectin (Scolantra) 1% cream applied once daily
    1. Very expensive (nearly $500 for 45 grams)
    2. (2015) Presc Lett 22(3): 16
  4. Minocycline 1.5% Foam (Zilxi)
    1. Very expensive (nearly $500 for 30 grams)
    2. No evidence of benefit over other Rosacea topicals
    3. (2021) Presc Lett 28(6): 36
    4. Stein Gold (2020) J Am Acad Dermatol 82(5): 1166-73 [PubMed]
Step 4: Refractory Cases
1. Topical Tretinoin (Retin A)
  1. May exacerbate erythema and Telangiectasis
2. Isotretinoin (Accutane)
  1. Requires IPledge registration (related to Teratogenicity risk)
  2. Administer 0.25 to 0.3 mg/kg/day (up to 0.5 mg/kg/day) for 20 weeks
  3. Variably effective in severe, refractory Rosacea; however more effective than Doxycycline
3. Consider mite or tinea management
  1. Examine sample with Potassium Hydroxide
  2. Crotamiton (Eurax)

Management
Facial Flushing and Erythema

First-line: See general measures above
Topical vasconstrictors (Alpha Adrenergic ReceptorAgonists
1. Activity
  1. Onset of action 30 minutes
  2. Peak effect in 3 to 6 hours
  3. Duration up to 12 hours
2. Brimonidine gel 0.33% (Mirvaso)
  1. Topical Vasoconstrictor released in 2013 in U.S.
  2. Can reduce facial redness (NNT 6 for significant benefit)
  3. May be more effective than Oxymetazoline
  4. Very expensive ($400 for 30 grams)
    1. Consider using generic Brimonidine 0.2% eye drops topically on face (10% of cost)
  5. References
    1. (2013) Presc Lett 20(11): 65
    2. Fowler (2013) J Drugs Dermatol 12(6): 650-6 [PubMed]
3. Oxymetazoline 1% (Rhofade)
  1. Topical Vasoconstrictor released in 2017 in U.S. (same ingredient as Afrin 0.05%, but 1%)
  2. Very expensive ($475 for 30 grams)
  3. References
    1. (2017) Presc Lett 24(5):30
    2. Baumann (2018) J Drugs Dermatol 17(3): 290-8 [PubMed]
Second-line
1. See Vasomotor Symptoms of Menopause
2. Propranolol (Inderal)
  1. Start with 10 mg immediate release orally three times daily
  2. May titrate as tolerated to 20 to 40 mg orally twice to three times daily
    1. Alternatively may use Propranolol LA 80 mg orally daily
3. Carvedilol (Coreg)
  1. Start with 3.125 mg immediate release tablet orally twice to three times daily
  2. May titrate as tolerated to 6.25 mg orally twice daily
  3. Maximum: 12.5 mg orally twice daily
4. Other agents that have been used for Flushing
  1. Clonidine 0.05 mg orally twice daily

Management
Ocular changes

Precautions
1. Risk of complications such as Chalazion, Scleritis, Corneal Ulcer
2. Consider ophthalmology Consultation
First-line therapy
1. Oral Doxycycline (or other oral Antibiotics listed above)
2. Artificial tears for eye dryness
3. Lid and lashes cleansing with baby Shampoo
4. Topical metrogel to Eyelid if involved
5. Omega-3 Fatty Acid Supplementation (inadequate evidence)
Second-line therapy for refractory cases
1. Ocular steroids (by ophthalmology)
2. Cyclosporine Ophthalmic Emulsion (Restasis) - by ophthalmology
3. Isotretinoin (Accutane)
References
1. Oltz (2011) Optometry 82(2): 92-103 [PubMed]
2. Vieira (2013) J Am Acad Dermatol 69 (suppl 1): S36-41 [PubMed]

Management
Other Rosacea Manifestations

Telangiectasis
1. Green-tinted cosmetics
2. Pulsed dye laser
Rhinophyma
1. Mild to moderate
  1. Antibiotics such as Doxycycline (as listed above)
  2. Oral Isotretinoin (Accutane)
2. Advanced cases (Surgery)
  1. Dermabrasion
  2. Hypertrophic tissue excision

References

(2021) Presc Lett 28(6): 36
Habif (1996) Clinical Dermatology, p. 182-4
Blount (2002) Am Fam Physician 66(3):435-40 [PubMed]
Frazier (2024) Am Fam Physician 109(6): 533-42 [PubMed]
Goldgar (2009) Am Fam Physician 80(5): 461-8 [PubMed]
Oge (2015) Am Fam Physician 92(3): 187-96 [PubMed]
Powell (2005) N Engl J Med 352(8):793-803 [PubMed]
Van Zuuren (2015) Cochrane Database Syst Rev (4): CD003262 [PubMed]
Van Zuuren (2019) Br J Dermatol 181(1): 65-79 [PubMed]
Zuber (2000) Prim Care 27(2):309-18 [PubMed]