Dermatology

Rosacea

Rosacea

Are You Confident of the Diagnosis?

  • Characteristic findings on physical examination

Primary clinical features (one or more) include: flushing, nontransient erythema, papules, and pustules and telangiectasias usually in a central facial distribution. There is a tendency for periocular skin to be spared.

There are four clinical subtypes: erythematotelangiectatic (ETR), papulopustular, glandular, and ocular.

Erythematotelangiectatic subtype (Figure 1):

Figure 1.

Erythematotelangiectatic subtype

  • Persistent erythema of the cheeks without preponderance of pustules and papules.

  • A history of flushing and blushing.

  • Erythema brought on by stimuli.

  • Often symptoms of burning and stinging.

  • Often intolerant of topically applied products.

Papulopustular subtype (Figure 2):

Figure 2.

Papulopustular subtype

  • Red central portion of the face with persistent or episodic inflammation characterized by small papules that may be surmounted by pinpoint pustules.

  • May have a history of flushing but less than in the ETR subtype.

  • Irritation from topically applied products not a constant feature.

  • May lead to chronic facial edema.

Glandular subtype (Figure 3):

Figure 3.

Phymatous complication of glandular subtype

  • Most common in men with thick sebaceous skin.

  • Edematous papules and independent pustules, often of large size.

  • Nodulocystic lesions may be present.

  • Often have a history of acne as an adolescent.

  • Usually an absence of complaints of burning and stinging from topical agents.

  • May be complicated by phymas.

Ocular subtype (Figure 4):

Figure 4.

Ocular subtype

  • Blepharitis and conjunctivitis are most common.

  • Recurrent chalazion and inflammation of meibomian glands may be present, as well as interpalpebral conjunctival hyperemia, conjunctival telangiectasias, watery or dry irritated eyes.

  • Symptoms include: burning, stinging, itching, light sensitivity, and foreign body sensation.

    • Expected results of diagnostic studies

Biopsy is usually not necessary. Histopathology shows vascular dilation of the upper and mid-dermal vessels with perivascular and perifollicular lymphohistiocytic inflammation. Superficial pustules can be seen. Histology is slightly different with each subtype reflecting the different clinical presentations. There is no laboratory benchmark.

  • Diagnosis confirmation

Exclude diagnoses of polycythemia vera, connective tissue disease, mastocytosis, photosensitivity, and chronic steroid application. Use laboratory testing specific for each of the prior diagnoses (such as CBC, ANA, serum tryptase, and phototesting). Take a thorough review of systems and a medication history to exclude these conditions. Extrafacial erythema is suggestive of an alternative diagnosis.

Who is at Risk for Developing this Disease?

Rosacea is more common in women than men, except for phymatous changes, which are more common in men. Age of onset is usually between 30-50 years and occurs more commonly in patients with fair skin and chronic solar damage.

What is the Cause of the Disease?

  • Etiology

Etiology is likely to be multifactorial. Genetics may play a role as up to 30% of patients have a family history of rosacea. In a twin study about half of the skin findings in rosacea are accounted for by genetics, the other half by environmental factors.

  • Pathophysiology

Pathophysiology is likely to be multifactorial; abnormal vasomotor responses to stimuli and chronic solar damage likely play a role in ETR and papulopustular subtypes. The glandular manifestations and the phymatous complication may be related to androgen stimulation.

Systemic Implications and Complications

Rosacea is a chronic inflammatory disease and recent studies have investigated the association with other inflammatory conditions. Cardiovascular disease was studied as inflammation is known to play a role in atherosclerosis. An association with dyslipidemia, as well as hypertension and an increased risk of coronary artery disease was noted in patients with rosacea. Gastroesophageal reflux disease may also have an increased incidence in rosacea patients. In addition, autoimmune conditions including type 1 diabetes, celiac disease, multiple sclerosis, and rheumatoid arthritis have recently been associated with rosacea. Further studies need to be conducted to validate and characterize these findings.

Rosacea has also been linked with migraines. In addition, patients with rosacea have higher incidences of depression, embarrassment, social anxiety, and decreased quality of life.

Potential cutaneous complications include:

  • Phymatous skin changes: Marked skin thickening and irregular surface nodularities on the nose (rhinophyma), chin (gnathophyma), forehead (metophyma), one or both ears (otophyma), and eyelids (blepharophyma).

  • Fibrosis of the skin secondary to compromise of facial lymphatic drainage.

  • Purplish-red suffusion of the central facial skin.

Complications can result from keratitis, iritis, and scleritis.

Treatment Options

GENERAL TREATMENT

Medical options: topicals

  • Mild cleansers.

  • Gentle moisturizers to maintain stratum corneum.

  • Sunscreens with physical blockers (titanium dioxide and zinc oxide).

  • Green or yellow-tinted makeup to help disguise erythema.

  • Avoid astringents, toners, menthols, camphor, products with sodium lauryl sulfate.

  • Avoid waterproof cosmetics and heavy foundations that are harder to apply and remove without irritating skin.

ERYTHEMATOTELANGIECTATIC SUBTYPE

Medical options: topicals

  • Azelaic acid daily (20% cream or 15% gel).

  • Sodium sulfacetamide-sulfur daily (10%-5%).

  • Mid to high-potency topical steroid ointment twice daily for only 1 week, followed by daily use for 1 week with addition of topical tacrolimus once daily, followed by cessation of steroid use with twice daily use of topical tacrolimus. (Topical pimecrolimus can also be used, however, patients often prefer the ointment base of topical tacrolimus.)

  • Brimonidine tartrate gel 0.33% daily (addresses the erythema but is not anti-inflammatory).

Medical options: systemics

  • For refractory facial flushing and persistent erythema in normotensive patients: low-dose carvedilol (3.25 mg three times daily titrated to 25 mg daily).

Surgical and other options: lasers

  • Pulsed dye laser or other vascular laser.

  • Intense pulsed light.

PAPULOPUSTULAR SUBTYPE

Medical options: topicals

  • Metronidazole 0.75% or 1% daily.

  • Sodium sulfacetamide-sulfur daily (10%-5%).

  • Azelaic acid daily (20% cream or 15% gel).

  • Tretinoin 0.025-0.1% cream nightly with moisturizer.

  • Ivermectin 1% cream daily.

Medical options: systemics

  • Systemic tetracyclines (tetracycline 250-500 mg daily-twice daily; minocycline 50-100 mg daily-twice daily; doxycycline 50-100 mg daily-twice daily; submicrobial dosing of doxycycline 20 mg twice daily or 40 mg delayed-release once daily).

  • If allergic or intolerant to tetracyclines, systemic macrolides can be used (erythromycin 250-500 mg daily-twice daily; azithromycin 250-500 mg thrice weekly).

  • Isotretinoin (used similarly as in acne with a goal cumulative dose of 120-150 mg/kg; may repeat the course after a 2-month break if lesions are not clear).

Surgical and other options: lasers

  • Pulsed dye laser or other vascular laser.

  • Intense pulsed light.

GLANDULAR SUBTYPE

Medical options: topicals

  • Benzoyl peroxide 2.5-5% daily.

  • Benzoyl peroxide-antibiotic combination products (combined with clindamycin, erythromycin, etc.,) daily.

  • Tretinoin 0.025-0.1% nightly cream.

  • Sodium sulfacetamide-sulfur daily (10%-5%).

  • Azelaic acid daily (20% cream or 15% gel).

Medical options: systemics

  • Systemic tetracyclines (tetracycline 250-500 mg daily-twice daily; minocycline 50-100 mg daily-twice daily; doxycycline 50-100 mg daily-twice daily; submicrobial dosing of doxycycline 20 mg twice daily or 40 mg delayed-release once daily).

  • If allergic or intolerant to tetracyclines, systemic macrolides can be used (erythromycin 250-500 mg daily-twice daily; azithromycin 250-500 mg thrice weekly).

  • Spironolactone 25-200 mg daily for women if papulopustular lesions predominate.

  • Oral contraceptive pills for women.

  • For phymatous patients: isotretinoin (used similarly as in acne with a goal cumulative dose of 120-150 mg/kg; may repeat the course after a 2-month break if lesions are not clear).

Surgical options

For phymatous patients: reshaping with laser ablation (carbon dioxide or erbium:yttrium-aluminum-garnet), dermabrasion, electrocautery, heated scalpel, tangential excision combined with scissor sculpturing, radiofrequency electrosurgery, or cryosurgery.

OCULAR SUBTYPE

Medical options: topicals

  • Lid hygiene: warm compresses, dilute baby shampoo scrubs, preservative-free lubricating eye drops.

  • Refer to ophthalmology for more severe disease to address inflammation (topical steroids), infection (topical antibiotics), or dry eyes (topical cyclosporine 0.05% drops twice daily to increase tear production).

Medical options: systemics

    • Systemic tetracyclines (tetracycline 250-500 mg daily-twice daily; minocycline 50-100 mg daily-twice daily; doxycycline 50-100 mg daily-twice daily; submicrobial dosing of doxycycline 20 mg twice daily or 40 mg delayed-release once daily).

    • If allergic or intolerant to tetracyclines, systemic macrolides can be used (erythromycin 250-500 mg daily-twice daily; azithromycin 250-500 mg thrice weekly).

    • Omega-3 fatty acid supplementation (decrease inflammation and improve the quality of meibomian gland secretion).

Optimal Therapeutic Approach for this Disease

Erythematotelangiectatic subtype

In the morning, use sodium sulfacetamide-sulfur cleanser followed by a moisturizing sunscreen and/or camouflaging cosmetic with sunscreen; in the evening, use azelaic acid or a sodium sulfacetamide-sulfur product. If possible from a financial point of view, vascular laser is a first-line therapy. If there is too much irritation or scale to begin any therapies, consider using the topical steroid/topical tacrolimus combination to help decrease inflammation.

There have been reports of some patients having short-term decreases in erythema using topical oxymetazoline (used similarly to brimonidine tartrate gel) but we do not generally recommend this for our patients. There is a risk of rebound erythema, flushing, and burning and it provides only short-term improvement.

Papulopustular subtype

In the morning, use topical metronidazole, azelaic acid, or sodium sulfacetamide-sulfur and a sunscreen; in the evening, use sodium sulfacetamide-sulfur cleanser and one of the preceding topical options listed for morning use. Use oral antibiotics or isotretinoin depending on severity.

Glandular subtype

The benzoyl peroxide-antibiotic combination is the most effective. Use oral antibiotics or isotretinoin depending on severity.

Ocular subtype

Encourage lid hygiene and refer to ophthalmology for more severe disease. Use oral antibiotics for moderate to severe ocular rosacea.

Patient Management

Most patients will need re-assessment in 2-3 months to evaluate therapy. Isotretinoin use will require more aggressive monitoring. If patients are not improving after 2-3 months, more aggressive therapy should be pursued. Patients should be educated that this is a chronic condition.

Unusual Clinical Scenarios to Consider in Patient Management

Patients that develop facial edema need to be closely monitored and treated aggressively to avoid solid facial edema.

For lymphedematous lesions, one of the authors (JC) has had success with cetirizine 10 mg daily or twice daily. Solid facial edema may respond to isotretinoin.

What is the Evidence?

Aksoy, B, Altaykan-Hapa, A, Egemen, D, Karagoz, F, Atakan, N. "The impact of rosacea on quality of life: effects of demographic and clinical characteristics and various treatment modalities". Br J Dermatol. vol. 163. 2010. pp. 719-25.

(A study of 308 patients with rosacea showing there was a moderate effect on the patient's quality of life and supporting, though not definitively, the positive effects of topical metronidazole, oral tetracycline, and oral isotretinoin on rosacea.)

Aldrich, N, Gerstenblith, M, Fu, P, Tuttle, MS, Varma, P, Gotow, E, Cooper, KD, Mann, M, Popkin, DL. "Genetic vs Environmental Factors That Correlate With Rosacea: A Cohort-Based Survey of Twins". JAMA Dermatol. vol. 151. 2015. pp. 1213-9.

(A study of 275 twin pairs with rosacea demonstrating that about half of their rosacea has a genetic contribution and the other half is due to environmental factors.)

Crawford, GH, Pelle, MT, James, WD. "Rosacea I: Etiology, pathogenesis, and subtype classification". J Am Acad Dermatol. vol. 51. 2004. pp. 327-41.

(A summary of the subtypes of rosacea with the clinical features that characterize each subgroup. It also collects the initial data on possible etiologies and pathophysiology of rosacea.)

Egeberg, A, Hansen, PR, Gislason, GH, Thyssen, JP. "Clustering of autoimmune diseases in patients with rosacea". J Am Acad Dermatol. vol. pii: S0190-9622. 2016 Jan 30. pp. 02465-2.

(Rosacea shares genetic risk loci with several autoimmune diseases. A Danish case-control study of 6759 patients with rosacea and 33,795 matched controls demonstrates an association between female patients with rosacea and type 1 diabetes, celiac disease, multiple sclerosis, and rheumatoid arthritis. The association in men was significant for rheumatoid arthritis.)

Hua, TC, Chung, PI, Chen, YJ, Wu, LC, Chen, YD, Hwang, CY, Chu, SY, Chen, CC, Lee, DD, Chang, YT, Liu, HN. "Cardiovascular comorbidities in patients with rosacea: A nationwide case-control study from Taiwan". J Am Acad Dermatol. vol. 73. 2015. pp. 249-54.

(A case-control study of 33,553 patients with rosacea and 67,106 age- and gender-matched control subjects demonstrate that patients with rosacea have an increased incidence of dyslipidemia. Hypertension and coronary artery disease is also associated. The incidence of peripheral arterial occlusive disease and cerebral infarction is increased in patients with rosacea but not statistically significant. Diabetes is not associated.)

Layton, A, Thiboutot, D. "Emerging therapies in rosacea". J Am Acad Dermatol. vol. 69. 2013. pp. S57-65.

(A review of low-dose antibiotics, beta-blockers, and antiparasitic agents for the treatment of rosacea.)

Madan, V, Ferguson, JE, August, PJ. "Carbon dioxide laser treatment of rhinophyma: a review of 124 patients". Br J Dermatol. vol. 161. 2009. pp. 814-8.

(A retrospective study of 124 patients treated with carbon dioxide laser for rhinophyma showing improvement with minimal side effects.)

Mansouri, Y, Goldenberg, G. "Devices and topical agents for rosacea management". Cutis. vol. 94. 2014. pp. 21-5.

(A review of devices and topical agents available for rosacea including light and laser devices and topical alpha-adrenergic receptor agonists.)

McAleer, MA, Fitzpatrick, P, Powell, FC. "Papulopustular rosacea: prevalence and relationship to photodamage". J Am Acad Dermatol. vol. 63. 2010. pp. 33-9.

(A study of 1000 Irish patients with papulopustular rosacea showing a prevalence of approximately 2.7%. UV radiation did not seem to play a role in prevalence in this population but it is unknown whether it worsens or affects the course of the disease.)

Moustafa, F, Lewallen, RS, Feldman, SR. "The psychological impact of rosacea and the influence of current management options". J Am Acad Dermatol. vol. 71. 2014. pp. 973-80.

(A review of the literature regarding the psychosocial and quality-of-life impact of rosacea was performed and revealed higher incidences of embarrassment, social anxiety, depression, and decreased quality of life in rosacea patients.)

Neuhaus, IM, Zane, LT, Tope, WD. "Comparative efficacy of nonpurpurogenic pulsed dye laser and intense pulsed light for erythematotelangiectatic rosacea". Dermatol Surg. vol. 35. 2009. pp. 920-8.

(A small, randomized, split face study comparing PDL and IPL treatments. Both therapies were effective and there was not a clear advantage to one or the other in terms of effectiveness.)

Pelle, MT, Crawford, GH, James, WD. "Rosacea II: Therapy". J Am Acad Dermatol. vol. 51. 2004. pp. 499-512.

(A therapeutic approach to rosacea with a focus on individual therapies and the data that support or do not support their use in rosacea.)

Rainer, BM, Fischer, AH, Luz Felipe da Silva, D, Kang, S, Chien, AL. "Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study". J Am Acad Dermatol. vol. 73. 2015. pp. 604-8.

(A case-control study of 65 rosacea patients and 65 controls demonstrated that moderate to severe rosacea is associated with hyperlipidemia, hypertension, metabolic diseases, cardiovascular disease, and gastroesophageal disease. Additional associations with allergies, respiratory disease, other gastrointestinal diseases, urogenital diseases, and female hormone imbalance were suggested; these categories encompassed many diseases and further statistical analyses of individual diseases was not provided.)

Ramelet, AA. "Rosacea: a reaction pattern associated with ocular lesions and migraine?". Arch Dermatol. vol. 130. 1994. pp. 1448.

(This study demonstrates an increased incidence of migraines in patients with rosacea. It was also found that women with rosacea were affected by migraines more than men. They also note that ocular symptoms were commonly associated with rosacea but did not specifically correlate with migraines.)

Vieira, AC, Mannis, MJ. "Ocular rosacea: common and commonly missed". J Am Acad Dermatol. vol. 69. 2013. pp. S36-41.

(A review of ocular rosacea with an overview of signs and symptoms and a therapeutic approach for the dermatologist.)
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