- Author: Agnieszka Kupiec Banasikowska, MD; Chief Editor: William D James, MD more...
Rosacea is a common condition characterized by symptoms of facial flushing and a spectrum of clinical signs, including erythema, telangiectasia, coarseness of skin, and an inflammatory papulopustular eruption resembling acne.[1, 2] See the image below.
Based on specific clinical signs and symptoms, an expert committee assembled by the National Rosacea Society explicitly defined and classified rosacea into the following subtypes:
Signs and symptoms
Central facial flushing, often accompanied by burning or stinging
Redness usually spares the periocular skin
Skin typically has a fine texture that lacks a sebaceous quality characteristic of other subtypes
Erythematous areas of the face at times appear rough with scale, likely due to chronic, low-grade dermatitis
Frequent triggers to flushing include acutely felt emotional stress, hot drinks, alcohol, spicy foods, exercise, cold or hot weather, and hot baths and showers
Patients report that the burning or stinging is exacerbated when topical agents are applied
This is the classic presentation of rosacea; features include the following:
Patients are typically women of middle age
Patients usually present with a red central portion of the face containing small erythematous papules surmounted by pinpoint pustules
Patient may describe a history of flushing
Telangiectasias are likely present but may be difficult to distinguish from the erythematous background in which they exist
Marked skin thickenings and irregular surface nodularities of the nose, chin, forehead, 1 or both ears, and/or the eyelids
Inflammation of the lids and meibomian glands
Interpalpebral conjunctival hyperemia
Although ocular manifestations may precede the cutaneous signs by years, in many cases they develop concurrently with dermatologic manifestations.
A rare granulomatous variant of rosacea (acne agminata/lupus miliaris disseminatus faciei) can manifest with inflammatory erythematous or flesh-colored papules distributed symmetrically across the upper part of the face, particularly around the eyes and the nose. The lesions tend to be discrete, and surrounding erythema is not a marked feature but may be present. These patients often do not have a history of flushing.
See Clinical Presentation for more detail.
The diagnosis of rosacea is made clinically, although a skin biopsy is sometimes performed to exclude other cutaneous diseases, such as lupus or sarcoidosis. Histologic findings include the following:
Nonpustular lesions show a nonspecific perivascular and perifollicular lymphohistiocytic infiltrate, accompanied by occasional multinucleated cells, plasma cells, neutrophils, and eosinophils
Papulopustular lesions demonstrate more pronounced granulomatous inflammation and sometimes perifollicular abscesses
Demodex folliculorum may be abundant in nearby follicles
The histologic features of granulomatous rosacea are striking, demonstrating caseating and noncaseating granulomata with negative stains for mycobacteria and fungi.
See Workup for more detail.
Vascular lasers, the mainstay of rosacea therapy, use wavelengths that allow selective absorption by oxyhemoglobin, leading to vessel reduction and causing minimal scarring or damage to surrounding tissue.
Permanent telangiectasia may be treated by electrosurgery or the 585-nm pulsed dye laser. However, facial erythema is not improved, and new telangiectasias develop with the passage of time.
Cosmetic improvement of rhinophyma may be produced by mechanical dermabrasion, carbon dioxide laser peel, and surgical shave techniques.
Before the initiation of therapy, the triggering factors that exacerbate the patient's rosacea should be identified and avoided if possible. Common triggering factors include the following[3, 4] :
Hot or cold temperatures
Topical products that irritate the skin and decrease the barrier
Medications that cause flushing
In addition, the use of daily broad-spectrum sunscreen is recommended for all patients with rosacea.
Rosacea is a common condition characterized by symptoms of facial flushing and a spectrum of clinical signs, including erythema, telangiectasia, coarseness of skin, and an inflammatory papulopustular eruption resembling acne.[1, 2]
An expert committee assembled by the National Rosacea Society explicitly defined and classified rosacea in April 2002 into 4 different subtypes (erythematotelangiectatic type, papulopustular, phymatous, and ocular) based on specific clinical signs and symptoms. This categorization was an important step in the treatment of rosacea. Currently, the therapeutics of rosacea empirically target the signs and symptoms of the disease because investigators do not understand the details of its pathophysiology. Therefore, this classification system aides clinicians in treatment by highlighting the preponderance of one or more of the clustering signs of presentation and, thus, helps to specify which therapeutic approach to initiate.
The diagnosis of rosacea is a clinical diagnosis. Skin biopsy may be necessary to exclude other disease states that mimic the clinical presentation of rosacea. For example, the clinician must exclude polycythemia vera, connective-tissue diseases (eg, lupus erythematous, dermatomyositis, mixed connective-tissue disease), photosensitivity, carcinoid syndrome, mastocytosis, long-term application of topical steroids, contact dermatitis, and photosensitivity before making the diagnosis of rosacea.
Rosacea is defined by persistent erythema of the central portion of the face lasting for at least 3 months. Supporting criteria include flushing, papules, pustules, and telangiectasias on the convex surfaces. Secondary characteristics are burning and stinging, edema, plaques, a dry appearance, ocular manifestations, and phymatous changes. The prevalence of these findings designates the subclassification of the presentation and, additionally, the therapeutic options.[6, 7, 8]
Central facial flushing, often accompanied by burning or stinging, is the predominant sign in erythematotelangiectatic rosacea (ETR). The redness usually spares the periocular skin. These patients typically have skin with a fine texture that lacks a sebaceous quality characteristic of other subtypes. The erythematous areas of the face at times appear rough with scale likely due to chronic, low-grade dermatitis. Frequent triggers to flushing include acutely felt emotional stress, hot drinks, alcohol, spicy foods, exercise, cold or hot weather, and hot baths and showers. These patients also report that the burning or stinging is exacerbated when topical agents are applied.
Papulopustular rosacea (PPR) is the classic presentation of rosacea. Patients are typically women of middle age who predominately present with a red central portion of their face that contains small erythematous papules surmounted by pinpoint pustules. One may elicit a history of flushing. Telangiectasias are likely present but may be difficult to distinguish from the erythematous background in which they exist. See the images below.
Phymatous rosacea is defined as marked skin thickenings and irregular surface nodularities of the nose, chin, forehead, one or both ears, and/or the eyelids. Four distinct histologic variants can occur with rhinophyma (associated changes of the nose) that include glandular, fibrous, fibroangiomatous, and actinic. The mainstays of treatment are isotretinoin topical application and surgical correction. This varies from other rosacea subtypes.
Ocular manifestations may precede the cutaneous signs by years. Yet, frequently they develop concurrently with dermatologic manifestations. The ocular manifestations include blepharitis, conjunctivitis, inflammation of the lids and meibomian glands, interpalpebral conjunctival hyperemia, and conjunctival telangiectasias. Patients may describe eye stinging or burning, dryness, irritation with light, or foreign body sensation. Ocular rosacea, similar to phymatous rosacea, has a distinct therapeutic management. Therefore, dermatologists must ask their patients specifically about ocular symptoms and perform a thorough physical examination to rule out this type of rosacea.
The etiology of rosacea is unknown. However, several factors, such as vasculature, climatic exposures, dermal matrix degeneration, chemicals and ingested agents, pilosebaceous unit abnormalities, microbial organisms, ferritin expression, reactive oxygen species (ROS), increased neoangiogenesis, and dysfunction of antimicrobial peptides (AMPs), likely play a role in its development. Furthermore, the distinct subtype of rosacea is likely determined by a patient's unique sensitivity to these triggers.
Increased blood flow to the blood vessels of the face and increased numbers of blood vessels that are closer to the surface of the face are thought to be responsible for the redness and flushing associated with rosacea. Furthermore, vasodilatation, the normal response to hyperthermia, is thought to be more pronounced or exaggerated in those individuals with rosacea.
Some evidence suggests that harsh climatic exposures damage cutaneous blood vessels and dermal connective tissue. This also includes exposure to solar irradiation, which may explain why rosacea predominately affects the facial convexities and has a tendency to flare in the spring. However, other studies suggest the contrary, in that most patients' symptoms do not worsen in the sunlight and do not flare with an acute exposure to ultraviolet (UV) light.
Dermal matrix degeneration
Rosacea involves associated damage to the endothelium and degeneration of the dermal matrix. However, it is not known whether the initial damage is in the dermal matrix and this leads to poor tissue support of cutaneous vessels, causing pooling of serum, inflammatory mediators, and metabolic waste, or whether the initial abnormality exists in the cutaneous vasculature and this leads to leaky vessels and delayed clearance of serum proteins, inflammatory mediators, and metabolic waste, thus resulting in matrix degeneration.
Chemicals and ingested agents
Spicy foods, alcohol, and hot beverages were traditionally thought to trigger flushing in patients with rosacea. However, most evidence does not support dietary factors playing a central role in the pathogenesis. Moreover, certain medications, such as amiodarone, topical steroids, nasal steroids, and high doses of vitamins B-6 and B-12, may cause flares for patients with rosacea.
Perivascular versus perifollicular inflammation
An inflammatory infiltrate may exist in a perivascular and/or a perifollicular location; however, evidence is conflicting regarding which location predominates. To answer this question, more studies need to be designed to categorize subtypes of rosacea because the answer varies depending on the subclassification.
Demodex species (mites that normally inhabit human hair follicles) may play a role in the pathogenesis of rosacea. Some studies suggest that Demodex prefers the skin regions that are affected in rosacea, such as the nose and cheeks. Research also supports that an immune response of helper-inducer T-cell infiltrates occurs, surrounding the Demodex antigens in patients with rosacea. Yet, conflicting evidence indicates that Demodex does not induce an inflammatory response in patients with rosacea. Moreover, Demodex is found in large numbers of healthy individuals without rosacea. More studies need to be performed to determine whether Demodex truly is pathogenic.
Additionally, inconclusive evidence suggests that Helicobacter pylori is associated with the etiology of rosacea. However, many of the studies have not controlled for confounding variables that influence H pylori prevalence, such as sex, age, socioeconomic status, and medications. Furthermore, these studies were not statistically powered to account for the ubiquitous nature of H pylori infection.
Iron catalyzes the conversion of hydrogen peroxide to free radicals, which leads to tissue injury by damaging cellular membranes, proteins, and DNA. At the cellular level, iron that is not metabolized is stored as ferritin. In a 2009 study, skin biopsy specimens from patients with rosacea were immunohistochemically analyzed, and the number of ferritin-positive cells was significantly higher in affected individuals compared with control subjects. Additionally, higher ferritin positivity correlated with more advanced subtypes of rosacea. Thus, increased release of free iron from proteolysis of ferritin can result in oxidative damage to the skin, which may contribute to the pathogenesis of rosacea.
Reactive oxygen species
Early in the inflammatory process, reactive oxygen species (ROS) are released by neutrophils, which are postulated to have a central role in the inflammation associated with rosacea. Free radicals, such as superoxide anions and hydroxyl radials, in addition to other reactive molecules, such as molecular oxygen, singlet oxygen, and hydrogen peroxide, comprise many of the ROS that lead to oxidative tissue damage. Several mechanisms explain how ROS result in skin inflammation, most notably the deactivation of natural defenses caused by excessive oxidant stress from ROS; chemical and oxidative modification of proteins and lipids by ROS; alteration of the lipid balance in rosacea patients, which, in normal proportions would suppress the creation of ROS; production of cytokines and other inflammatory mediators by keratinocytes, fibroblasts, and endothelial cells damaged by ROS; and the generation of ROS by cathelicidins, which are found in greater amounts in the facial skin of affected individuals.
Neoangiogenesis and vascular endothelial growth factor (VEGF) overexpression
Studies performed using video capillaroscopy on erythematotelangiectatic rosacea lesions showed increased neoangiogenesis and blood vessel enlargement. Multiple immunohistochemistry studies showed increased VEGF expression in vascular endothelium in lesional versus nonlesional skin of rosacea patients. Cuevas et al used topical dobesilate, an inhibitor of angiogenic growth factor, for the treatment of erythematotelagiectatic rosacea and reported an improvement in erythema and telangiectasia after 2 weeks.
AMPs are small molecular weight proteins that are a part of the innate immune response and have demonstrated broad-spectrum antimicrobial activity against bacteria, viruses, and fungi. They are rapidly released upon injury and/or infection of the skin, and they have been implicated in the pathogenesis of many inflammatory skin diseases. Cathelicidins and β-defensins are 2 well-known types of AMPs, of which the former has been shown to be expressed in abnormally high levels in patients with rosacea.
Specifically, the LL-37 peptide form of cathelicidin, in addition to proteolytically processed forms of LL-37, have been found in significantly different amounts in rosacea patients compared with healthy individuals. LL-37 is expressed by polymorphonuclear leukocytes and lymphocytes. LL-37 interacts with endothelial cells and stimulates angiogenesis both in vitro and in vivo. It also modulates the expression of VEGF. Injection of LL-37 and these novel peptides derived from LL-37 into mice induced inflammation, erythema, and telangiectasia; therefore, researchers hypothesized that an excess of cathelicidins coupled with abnormal processing caused disease.
Accurate incidence data are not available; however, rosacea is a common skin condition that disproportionately affects persons of fair-skinned European and Celtic origin. A study in Sweden revealed an incidence of 1 in 10 middle-class workers. The caseating granulomatous variant (acne agminata) may more commonly occur in people of Asian or African origin.
A spectrum of clinical features is seen, and progression may be step-wise. The condition ranges from minor cosmetic disability to severe disfiguring disease. In most patients who receive treatment, a stable state is reached with variable residual symptomatology. The disease takes a chronic relapsing or progressive course for some patients.
Patients should be advised to avoid known exacerbating factors, such as hot or cold temperatures, wind, hot drinks, caffeine, exercise, spicy food, alcohol, strong emotions, topical products that irritate the skin and decrease the barrier, and medications that cause flushing. Patients should be encouraged to use a noncomedogenic, high-factor sunscreen when exposed to sunlight and wind.
For patient education resources, see the Skin Conditions and Beauty Center.
Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015 May. 72 (5):749-58; quiz 759-60. [Medline].
Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part II. Topical and systemic therapies in the treatment of rosacea. J Am Acad Dermatol. 2015 May. 72 (5):761-70; quiz 771-2. [Medline].
Greaves MW, Burova E. Flushing: causes, investigation and clinical consequences. J Eur Acad Dermatol Venereol. 1997. 8:91-100.
Higgins E, du Vivier A. Alcohol intake and other skin disorders. Clin Dermatol. 1999 Jul-Aug. 17(4):437-41. [Medline].
Powell FC. Clinical practice. Rosacea. N Engl J Med. 2005 Feb 24. 352(8):793-803. [Medline].
Bamford JT, Gessert CE, Renier CM. Measurement of the severity of rosacea. J Am Acad Dermatol. 2004 Nov. 51(5):697-703. [Medline].
Crawford GH, Pelle MT, James WD. Rosacea: I. Etiology, pathogenesis, and subtype classification. J Am Acad Dermatol. 2004 Sep. 51(3):327-41; quiz 342-4. [Medline].
Dahl MV. Rosacea subtypes: a treatment algorithm. Cutis. 2004 Sep. 74(3 Suppl):21-7, 32-4. [Medline].
Laquer V, Hoang V, Nguyen A, Kelly KM. Angiogenesis in cutaneous disease: part II. J Am Acad Dermatol. 2009 Dec. 61(6):945-58; quiz 959-60. [Medline].
Bonnar E, Eustace P, Powell FC. The Demodex mite population in rosacea. J Am Acad Dermatol. 1993 Mar. 28(3):443-8. [Medline].
Tisma VS, Basta-Juzbasic A, Jaganjac M, et al. Oxidative stress and ferritin expression in the skin of patients with rosacea. J Am Acad Dermatol. 2009 Feb. 60(2):270-6. [Medline].
Jones DA. Rosacea, reactive oxygen species, and azelaic acid. J Clin Aesthetic Derm. Jan 2009. 2(1):26-30.
Cuevas P, Arrazola JM. Therapeutic response of rosacea to dobesilate. Eur J Med Res. 2005 Oct 18. 10(10):454-6. [Medline].
Schauber J, Gallo RL. Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol. 2008 Aug. 122(2):261-6. [Medline].
Aloi F, Tomasini C, Soro E, Pippione M. The clinicopathologic spectrum of rhinophyma. J Am Acad Dermatol. 2000 Mar. 42(3):468-72. [Medline].
Lonne-Rahm S, Nordlind K, Edstrom DW, Ros AM, Berg M. Laser treatment of rosacea: a pathoetiological study. Arch Dermatol. 2004 Nov. 140(11):1345-9. [Medline].
Ceilley RI. Advances in the topical treatment of acne and rosacea. J Drugs Dermatol. 2004 Sep-Oct. 3(5 Suppl):S12-22. [Medline].
Ertl GA, Levine N, Kligman AM. A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea. Arch Dermatol. 1994 Mar. 130(3):319-24. [Medline].
Gupta AK, Chaudhry MM. Rosacea and its management: an overview. J Eur Acad Dermatol Venereol. 2005 May. 19(3):273-85. [Medline].
Fowler J Jr, Jackson M, Moore A, Jarratt M, Jones T, Meadows K, et al. Efficacy and Safety of Once-Daily Topical Brimonidine Tartrate Gel 0.5% for the Treatment of Moderate to Severe Facial Erythema of Rosacea: Results of Two Randomized, Double-blind, and Vehicle-Controlled Pivotal Studies. J Drugs Dermatol. 2013 Jun 1. 12(6):650-6. [Medline].
Stein L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014 Mar. 13(3):316-23. [Medline].
Allen KJ, Davis CL, Billings SD, Mousdicas N. Recalcitrant papulopustular rosacea in an immunocompetent patient responding to combination therapy with oral ivermectin and topical permethrin. Cutis. 2007 Aug. 80(2):149-51. [Medline].
Forstinger C, Kittler H, Binder M. Treatment of rosacea-like demodicidosis with oral ivermectin and topical permethrin cream. J Am Acad Dermatol. 1999 Nov. 41(5 Pt 1):775-7. [Medline].
Karincaoglu Y, Bayram N, Aycan O, Esrefoglu M. The clinical importance of demodex folliculorum presenting with nonspecific facial signs and symptoms. J Dermatol. 2004 Aug. 31(8):618-26. [Medline].
Brown M, Hernández-Martín A, Clement A, Colmenero I, Torrelo A. Severe demodexfolliculorum-associated oculocutaneous rosacea in a girl successfully treated with ivermectin. JAMA Dermatol. 2014 Jan. 150(1):61-3. [Medline].
Galderma. Randomized, double-blind, parallel-group, vehicle-controlled, dose-finding study investigating the pharmacodynamics and safety of three concentrations of CD07805/47 topical gel (0.07%, 0.18%, and 0.50%), applied in subjects with moderate to severe erythematotelangiectatic rosacea. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT00989014. Accessed: August 21, 2014.
Galderma. A phase 3 randomized, double blind, 12 week vehicle controlled, parallel group study assessing the efficacy and safety of CD5024 1 % cream versus vehicle cream in subjects with papulopustular rosacea, followed by a 40 week investigator blinded extension comparing the long term safety of CD5024 1% cream versus azelaic Acid 15 % gel. ClinicalTials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT01493687. Accessed: August 21, 2014.
Galderma. Efficacy and safety of CD5024 1% cream versus metronidazole 0.75% cream in subjects with papulopustular rosacea over 16 weeks treatment, followed by a 36-week extension period (ATTRACT). ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT01493947. Accessed: August 21, 2014.
Baldwin HE. Systemic therapy for rosacea. Skin Therapy Lett. 2007 Mar. 12(2):1-5, 9. [Medline].
Chu CY. The use of 1% pimecrolimus cream for the treatment of steroid-induced rosacea. Br J Dermatol. 2005 Feb. 152(2):396-9. [Medline].
van Zuuren EJ, Kramer S, Carter B, Graber MA, Fedorowicz Z. Interventions for rosacea. Cochrane Database Syst Rev. 2011 Mar 16. 3:CD003262. [Medline].