eMedicine Specialties > Dermatology > Diseases of the Adnexa
Rosacea
Updated: Jun 12, 2009
Introduction
Background
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.
Definition and subtypes
An expert committee assembled by the National Rosacea Society explicitly defined and classified rosacea in April 2002 into 4 different subtypes 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.1,2,3
Erythematotelangiectatic type
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
Papulopustular rosacea (PPR) is the classic presentation of rosacea. Patients are 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.
Acne rosacea. Courtesy of Dirk Elston, MD.
Pustular rosacea. Courtesy of Dirk Elston, MD.
Phymatous rosacea
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 rosacea
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.
Pathophysiology
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), 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.
Vasculature
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.
Climatic exposures
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 may trigger a flushed face 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.
Microbial organisms
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.4 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.
Ferritin expression
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.5
Reactive oxygen species
Early in the inflammatory process, 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.6
Antimicrobial peptides
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. 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.7
Frequency
United States
Accurate incidence data are not available, but persons with rosacea are disproportionately of fair-skinned European and Celtic origin.
International
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.
Mortality/Morbidity
A spectrum of clinical features is seen, and progression may be step-wise. The condition ranges from minor cosmetic disability to severe disfiguring disease.
Clinical
History
Patients are likely to have a background of facial flushing, often dating to childhood or the early teens. In adult life, flushing may be increasingly precipitated by hot drinks, heat, emotion, and other causes of rapid body temperature changes. Some patients report flushing with alcohol, which is not specific.
The symptoms are usually intermittent but can progressively lead to permanently flushed skin. The latter may be described as high color and is associated with the development of permanent telangiectasia. Additionally, a few individuals report a gritty quality of the eyes and facial edema.
Physical
The disease consists of a spectrum of symptoms and signs, with most patients failing to develop every stage of disease. Variable erythema and telangiectasia are seen over the cheeks and the forehead. Inflammatory papules and pustules may be predominantly observed over the nose, the forehead, and the cheeks. Extrafacial involvement uncommonly occurs over the neck and the upper part of the chest. Prominence of sebaceous glands may be noted, with the development of thickened and disfigured noses (rhinophyma) in extreme cases. Unlike acne, patients generally do not report greasiness of the skin; instead, they may experience drying and peeling. The absence of comedones is another helpful distinguishing feature. Ocular lymphedema may be prominent but is uncommon. The condition generally does not produce scarring.
- Rhinophyma may occur as an isolated entity, without other symptoms or signs of rosacea. Rhinophyma can be disfiguring and therefore distressing for patients. Some authorities consider rhinophyma to represent a different disease process.8
- Lymphedema may be marked periorbitally, and, on occasion, it is the presenting symptom.
- Symptoms of ocular rosacea may be accompanied by conjunctival injection, and, rarely, chalazion and episcleritis may occur.
- Rosacea fulminans (pyoderma faciale) is fortunately a rare complication and is characterized by the development of nodules and abscesses with sinus tract formation accompanied by systemic signs.
- Both seborrhea and seborrheic dermatitis/blepharitis are not uncommonly observed in patients with rosacea. The reasons for these associations are not well understood.
- A rare caseating 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. This pattern of rosacea is sometimes associated with scarring and may be resistant to conventional treatment.
Lupus miliaris disseminatus faciei. Courtesy of Dirk Elston, MD.
Causes
A rosacealike syndrome (including perioral dermatitis) can result from the indiscriminate use of potent corticosteroids on the face. A number of aggravating factors may be recognized. Excess wind and UV light (weathering) exposure may accelerate the disease process. See Pathophysiology for more information.
Differential Diagnoses
Lupus Erythematosus, Acute
Perioral Dermatitis
Sarcoidosis
Seborrheic Dermatitis
Other Problems to Be Considered
The differential diagnosis largely depends on the pattern of rosacea. Erythematotelangiectatic rosacea (ETR) can resemble seborrheic dermatitis, lupus erythematosus, and other photodermatoses. Carcinoid syndrome and mitral valve incompetence are overlooked causes of erythema and telangiectasia. Acneiform rosacea may be simulated by acne, bromoderma and iododerma, perioral dermatitis, and pustular folliculitis. Acne agminata can be indistinguishable from lupus vulgaris and cutaneous sarcoidosis.
Workup
Laboratory Studies
The diagnosis is made clinically.
Procedures
A skin biopsy is sometimes performed to exclude other cutaneous diseases, such as lupus or sarcoidosis.
Histologic Findings
The histologic features of rosacea depend on the stage of disease. 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 acne agminata are striking, demonstrating caseating granulomata with negative stains for mycobacteria and fungi.
Histopathology of rosacea. Perifollicular chronic inflammation and vascular ectasia. Courtesy of Dirk Elston, MD.
Caseating granuloma in lupus miliaris disseminatus faciei. Courtesy of Dirk Elston, MD.
Treatment
Medical Care
Before the initiation of therapy, the triggering factors that exacerbate the patient's rosacea should be identified and avoided if possible. These factors may be unique to each individual patient. Common triggering factors include hot or cold temperatures, wind, hot drinks, caffeine, exercise, spicy food, alcohol, emotions, topical products that irritate the skin and decrease the barrier, or medications that cause flushing.9,10 Some patients find that regular facial massage reduces lymphedema. Rosacea fulminans is treated with moderately high doses of prednisolone (30-60 mg/d) followed by oral isotretinoin.
Sunscreen11
The use of daily broad-spectrum sunscreen is recommended for all patients with rosacea. A sunscreen that protects against both UV-A and UV-B light should be selected. Physical blockers such as titanium dioxide and zinc oxide are well tolerated. Additionally, the sunscreen should contain protective silicones such as dimethicone or cyclomethicone. Green-tinted sunscreens can provide coverage of the erythema.
The patient is encouraged to avoid astringents, toners, menthols, camphor, waterproof cosmetics requiring solvents for removal, or products containing sodium lauryl sulfate.
Laser12
Nonablative laser is effective against rosacea by remodeling of the dermal connective tissue and improving the epidermal barrier. The major disadvantage of this therapy is its cost because it is not covered by insurance. It requires 1-3 treatments 4-8 weeks apart to achieve the best results.
Vascular lasers are the mainstay of rosacea therapy. These include pulsed dye laser (585 or 595 nm), the potassium-titanyl-phosphate laser (532 nm), and the diode-pumped frequency-doubled laser (532 nm). These wavelengths allow selective absorption by oxyhemoglobin, leading to vessel reduction with minimal damage to surrounding tissue or scarring. To be effective against deeper facial vessels, longer wavelengths of lasers are required, including the diode laser (810 nm), the long-pulsed Alexandrite laser (755 nm), and the long-pulsed Nd:YAG laser (1064 nm).
Intense pulsed-light therapy is a multichromatic laser with different targets, including melanin and hemoglobin. Therefore, it is also useful for facial rejuvenation, affecting vascular lesions, pigmented lesions, and hair.
Surgical Care
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.
Diet
Dietary modulation should aim at avoidance of triggers.
Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Topical metronidazole is commonly used as a first-line agent. Topical azelaic acid, sulfacetamide products, and topical acne medications are also commonly used. Retinoids are advocated by some authorities.13,14,15
In addition to the agents listed below, anecdotal evidence indicates effective treatment of rosacea with medications that reduce flushing, including beta-blockers, clonidine, naloxone, ondansetron, and selective serotonin reuptake inhibitors.
Oral contraceptive therapy has been helpful in patients who provide historical information of worsening rosacea with their hormonal cycle.
Dapsone has been used in severe, refractory rosacea, and dapsone has been particularly beneficial for patients who cannot take isotretinoin.16
Immunosuppressants
These agents inhibit immune reactions resulting from diverse stimuli.17
Tacrolimus (Protopic) ointment 0.1% or 0.03%
Mechanism of action in atopic dermatitis not known. Reduces itching and inflammation by suppressing release of cytokines from T cells. Also inhibits transcription of genes encoding IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, all of which are involved in early stages of T-cell activation. Additionally, may inhibit release of preformed mediators from skin mast cells and basophils, and may down-regulate expression of FCeRI on Langerhans cells. Can be used in patients as young as 2 y. Drugs of this class are more expensive than topical corticosteroids. Available as ointment in concentrations of 0.03% and 0.1%. Indicated only after other treatment options have failed.
Dosing
Adult
Apply thin layer to affected skin areas bid.
Pediatric
<2 years: Not established
2-15 years: Apply 0.03% ointment bid to affected area(s)
>15 years: Administer as adults
Short-term and intermittent use only
Interactions
None reported
Contraindications
Documented hypersensitivity to tacrolimus or components of ointment
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Patients may experience a burning sensation during first few days of application; may cause rosacealike eruption, and patients must be monitored; skin can become photosensitive, and patients should be cautioned about exposure to direct or artificial sunlight and to use sunscreen; safety and efficacy in infected atopic dermatitis is not known; application under occlusion, which may promote systemic exposure, has not been evaluated (do not use with occlusive dressings)
Absorption following topical applications is minimal (relative to systemic administration), but tacrolimus is excreted in human milk and, thus, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account importance of drug to mother (potential for serious adverse reactions in nursing infants should also be a concern)
Caution with conditions that suppress immune system (eg, AIDS, cancer); possible risk of lymph node or skin cancer based on animal studies and a small number of patients; may increase risk of viral infections; other adverse effects include headache, sore throat, flulike symptoms, fever, and cough
Antibiotics
Since the 1950s, oral antibiotics have been prescribed off label for treatment because microorganisms were thought to be the underlying cause of disease. In current practice, experts do not believe bacterial infection plays a part in the pathogenesis of rosacea; however, the observed clinical benefits of oral antibiotics have allowed this treatment option to remain in favor for both physicians and patients. Since 2006, nonantibiotic dosing of doxycycline has become first-line treatment for many clinicians. In many cases, oral and topical antibiotics are used in combination; the oral treatment is eventually withdrawn and the topical treatment is used alone as maintenance therapy.16
Azithromycin (Zithromax)
Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl tRNA from ribosomes, causing bacterial growth inhibition.
Dosing
Adult
500 mg PO on day 1, followed by 250 mg PO qd for next 4 d
Pediatric
Not established
Interactions
Toxicity increases with coadministration of fluconazole and pimozide; effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, carbamazepine, ergot alkaloids, triazolam, and HMG-CoA reductase inhibitors
Plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increases in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents; decreases metabolism of repaglinide, thus increasing serum levels and effects
Contraindications
Documented hypersensitivity; coadministration of pimozide; hepatic impairment
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function or prolonged QT intervals
Metronidazole gel 0.75% or 1% (MetroGel, Noritate, Flagyl, Protostat)
Imidazole ring–based antibiotic active against various anaerobic bacteria and protozoa.
Oral metronidazole has been shown to be beneficial against papules and pustules of acne rosacea.
Topical applications are helpful for mild disease and as an adjuvant to systemic therapy.
Dosing
Adult
Oral: 200 mg bid
Topical: Wash affected area and apply a thin film to affected area bid
Pediatric
Oral: 15-35 mg/kg/d divided q8h
Topical: Apply as in adults
Interactions
May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy; gel dosage form is for external use only; do not apply directly to eyes
Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab) tab or 2% topical solution
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.
Can be used when tetracyclines are not tolerated or are contraindicated.
Used for the treatment of ocular rosacea.
Dosing
Adult
Oral: 500 mg bid
Topical: Apply to affected area bid for 2 wk
Pediatric
Oral: 30-50 mg/kg/d divided qid
Topical: Apply as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue if irritation or sensitivity occurs
Fusidic acid (Fucithalmic)
Ophthalmic susp as 10 mg/g (1%) (0.2 g) unit-dose, without preservative; 3 g and 5 g in multidose contains benzalkonium chloride.
For the treatment of ocular rosacea. Topical antibacterial that inhibits bacterial protein synthesis, causing bacterial death. Rosacea may respond to topical fusidic acid for at least 3 mo.
Dosing
Adult
Apply to affected area bid for 2 wk
Pediatric
Apply as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue if irritation or sensitivity occur
Clindamycin lotion or gel 1%
Semisynthetic antibiotic produced by 7(S)-chloro substitution of 7(R)-hydroxyl group of parent compound lincomycin. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Widely distributes in body without penetration of CNS. Protein bound and excreted by liver and kidneys.
Upon application to skin, drug is converted to active component, which inhibits the microorganism.
Available as topical solution, lotion, or gel for external use. Solution contains equivalent of 10 mg/mL clindamycin.
Effective against mild-to-moderate papulopustular rosacea.
Dosing
Adult
Apply to affected area qd
Pediatric
Apply as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Prolonged use may result in overgrowth of nonsusceptible organisms (eg, fungi); discontinue use if superinfection occurs
Tetracycline (Sumycin)
Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s). Has anti-inflammatory activity. Improvement is evident within 2-4 mo after commencement of therapy.
Dosing
Adult
250 mg PO qd to 500 mg PO tid
Pediatric
<8 years: Not recommended
>8 years: 25-50 mg/kg/d (10-20 mg/lb) PO qid
Interactions
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Contraindications
Documented hypersensitivity; severe hepatic dysfunction
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Minocycline (Dynacin, Minocin)
Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma.
Dosing
Adult
50-100 mg PO qd/bid
Pediatric
<8 years: Not recommended
>8 years: 4 mg/kg PO initially, followed by 2 mg/kg q12h
Interactions
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Contraindications
Documented hypersensitivity; severe hepatic dysfunction
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; hepatitis or lupuslike syndromes may occur
Doxycycline (Oracea, Bio-Tab, Doryx, Periostat, Vibramycin)
Broad-spectrum, synthetically derived, bacteriostatic antibiotic in tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Dosing
Adult
40-100 mg PO qd/bid
Pediatric
<8 years: Not recommended
>8 years: 2-5 mg/kg/d PO in 1-2 divided doses; not to exceed 200 mg/d
Interactions
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants.
Contraindications
Documented hypersensitivity; severe hepatic dysfunction
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Clarithromycin (Biaxin)
Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl tRNA from ribosomes, causing bacterial growth inhibition.
Dosing
Adult
250 mg PO bid
Pediatric
Not established
Interactions
Coadministration with pimozide, cisapride, or moxifloxacin may increase risk of malignant arrhythmias; toxicity increases with coadministration of fluconazole or pimozide; effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, carbamazepine, ergot alkaloids, triazolam, and HMG-CoA reductase inhibitors
Plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increases in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents; decreases metabolism of repaglinide, thus increasing serum levels and effects
Contraindications
Documented hypersensitivity; coadministration with pimozide, ergot derivatives, or cisapride
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzyme levels and cholestatic jaundice; caution in patients with prolonged QT intervals or pneumonia; give half dose or increase dosing interval if CrCl <30 mL/min; caution in hospitalized, geriatric, or debilitated patients
Retinoids
These agents decrease the cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for malignant degeneration. They modulate keratinocyte differentiation, and they have been shown to reduce the risk of skin cancer formation in patients who have undergone renal transplantation.
Tretinoin (Avita, Retin-A, Retin-A Micro)
Structurally related to vitamin A. May be helpful for recalcitrant disease, but recurrence is common. Long-term, low-dose therapy may be suitable for selected patients.
May cause skin irritation in some patients. Has been linked to promotion of angiogenesis; however, has not demonstrated increased telangiectasias.
Inhibits microcomedo formation and eliminates lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Available also as 0.01% and 0.025% gels.
Dosing
Adult
Begin with lowest concentration and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops
Pediatric
<12 years: Not established
>12 years: Apply as in adults
Interactions
Toxicity may occur with vitamin A coadministration; toxicity increased when coadministered with sulfur, benzoyl peroxide, resorcinol, or any product with strong drying effects; phototoxicity increased when coadministered with tetracyclines, fluoroquinolones, or thiazides
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with excessive sunlight exposure; burning, stinging, peeling, pruritus, or erythema has been reported at site of application; caution with eczema (may cause severe irritation); avoid contact with mucous membranes, mouth, and angles of nose
Isotretinoin (Accutane)
Oral agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of naturally occurring tretinoin (trans -retinoic acid). May be helpful for recalcitrant disease, but recurrence is common. Long-term, low-dose therapy may be suitable for selected patients.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Dosing
Adult
0.5-1 mg/kg/d PO divided bid for 4 mo
Pediatric
Not established
Interactions
Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine and contraceptive efficacy
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting) may occur
Diabetes patients may experience problems in controlling blood glucose while on isotretinoin; avoid exposure to UV light or sunlight until tolerance achieved; discontinue treatment if rectal bleeding, abdominal pain, or severe diarrhea occur
Mood swings or depression may occur; caution if history of depression
Corticosteroids
These agents are relatively contraindicated, except as a short course in rosacea fulminans.
Prednisolone (AK-Pred, Delta-Cortef, Articulose-50, Econopred)
Moderately high doses may be helpful in rosacea fulminans. Decreases inflammation by suppressing migration of PMN leukocytes and reducing capillary permeability. Use in combination with isotretinoin. Rosacea fulminans is treated with moderately high doses of prednisolone (30-60 mg/d) followed by oral isotretinoin.
Dosing
Adult
30-60 mg PO qd
Pediatric
0.1-2 mg/kg/d PO qd or divided tid/qid
Interactions
Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects
Contraindications
Documented hypersensitivity; viral, fungal, or tubercular skin lesions
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes mellitus, and myasthenia gravis
Antihypertensive agents
Potassium-sparing diuretics can be used to reduce morbidity.
Spironolactone (Aldactone)
Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.
Aldosterone inhibitors help block the renin-angiotensin system and help prevent potassium loss in distal tubules. The body conserves potassium, and less oral potassium supplementation is needed.
Dosing
Adult
50 mg PO qd
Pediatric
Not established
Interactions
May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity of spironolactone
Contraindications
Documented hypersensitivity; anuria; renal failure; hyperkalemia
Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal and hepatic impairment
Acne Products
Some products in this category can be effective in patients with papules, pustules, and the phymatous and glandular types of rosacea.
Benzoyl peroxide (Benoxyl, Benzac, Oxy-5, Fostex)
Free-radical oxygen is released upon administration and oxidizes bacterial proteins in sebaceous follicles, decreasing quantity of irritating free fatty acids and of anaerobic bacteria. Converted on skin into benzoic acid, which has keratolytic and comedolytic effects. However, can be quite irritating in patients with barrier dysfunction and can cause further erythema. Available over the counter and by prescription.
Available in 2.5%, 5%, and 10% gels, lotions, creams, or washes.
Dosing
Adult
Apply sparingly qd; gradually increase to bid/tid prn; reduce dose, frequency, or concentration if excessive dryness or peeling occurs
Pediatric
Not established
Interactions
Potentiates adverse effects of tretinoin
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Avoid contact with lips, eyelids, mucous membranes, and eyes; for external use only; discontinue if swelling, burning, or excessive dryness occurs
Azelaic acid (Azelex, Finacea)
Available in 2 strengths azelaic acid 15% gel (Finacea) or azelaic acid 20% cream (Azelex). Effective against mild-to-moderate papulopustular rosacea. Can be used twice daily as initial treatment. May reduce production of ROS by neutrophils. Some patients report transient burning or stinging.
Dosing
Adult
Wash area and apply sparingly bid; duration of use can vary from person to person and depends on severity of acne
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Avoid contact with eyes; discontinue use if severe irritation develops
Sodium sulfacetamide and sulfur (Plexion, Clenia, Rosanil wash, Rosula gel or wash, Rosac cream, Sulfacet-R lotion, Clarifoam EF)
Contains 5% sulfur and 10% sodium sulfacetamide. Used topically for acne rosacea. Sodium sulfacetamide has antibacterial properties, whereas sulfur is considered an antiseptic with keratolytic action.
Dosing
Adult
Apply to affected area; do not apply to irritated or abraded skin
Pediatric
Not established
Interactions
None reported
Contraindications
Documented hypersensitivity; renal failure
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not apply to irritated or abraded skin and avoid eyes; may cause local irritation (eg, stinging, burning, itching); may cause photosensitization; for external use only
Follow-up
Complications
- Rosacea keratitis and keratoconjunctivitis sicca are recognized complications.
- Rosacea fulminans is a rare complication.
- Scarring generally does not occur.
Prognosis
- 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.
Patient Education
- 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 excellent patient education resources, see eMedicine's Skin, Hair, and Nails Center.
Multimedia
Media file 1: Acne rosacea. Courtesy of Dirk Elston, MD.
Media file 2: Pustular rosacea. Courtesy of Dirk Elston, MD.
Media file 3: Histopathology of rosacea. Perifollicular chronic inflammation and vascular ectasia. Courtesy of Dirk Elston, MD.
Media file 4: Lupus miliaris disseminatus faciei. Courtesy of Dirk Elston, MD.
Media file 5: Caseating granuloma in lupus miliaris disseminatus faciei. Courtesy of Dirk Elston, MD.
References
Bamford JT, Gessert CE, Renier CM. Measurement of the severity of rosacea. J Am Acad Dermatol. Nov 2004;51(5):697-703. [Medline].
Crawford GH, Pelle MT, James WD. Rosacea: I. Etiology, pathogenesis, and subtype classification. J Am Acad Dermatol. Sep 2004;51(3):327-41; quiz 342-4. [Medline].
Dahl MV. Rosacea subtypes: a treatment algorithm. Cutis. Sep 2004;74(3 Suppl):21-7, 32-4. [Medline].
Bonnar E, Eustace P, Powell FC. The Demodex mite population in rosacea. J Am Acad Dermatol. Mar 1993;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. Feb 2009;60(2):270-6. [Medline].
Jones DA. Rosacea, reactive oxygen species, and azelaic acid. J Clin Aesthetic Derm. Jan 2009;2(1):26-30.
Schauber J, Gallo RL. Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol. Aug 2008;122(2):261-6. [Medline].
Aloi F, Tomasini C, Soro E, Pippione M. The clinicopathologic spectrum of rhinophyma. J Am Acad Dermatol. Mar 2000;42(3):468-72. [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. Jul-Aug 1999;17(4):437-41. [Medline].
Powell FC. Clinical practice. Rosacea. N Engl J Med. Feb 24 2005;352(8):793-803. [Medline].
Lonne-Rahm S, Nordlind K, Edstrom DW, Ros AM, Berg M. Laser treatment of rosacea: a pathoetiological study. Arch Dermatol. Nov 2004;140(11):1345-9. [Medline].
Ceilley RI. Advances in the topical treatment of acne and rosacea. J Drugs Dermatol. Sep-Oct 2004;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. Mar 1994;130(3):319-24. [Medline].
Gupta AK, Chaudhry MM. Rosacea and its management: an overview. J Eur Acad Dermatol Venereol. May 2005;19(3):273-85. [Medline].
Baldwin HE. Systemic therapy for rosacea. Skin Therapy Lett. Mar 2007;12(2):1-5, 9. [Medline].
Chu CY. The use of 1% pimecrolimus cream for the treatment of steroid-induced rosacea. Br J Dermatol. Feb 2005;152(2):396-9. [Medline].
Keywords
rosacea, acne rosacea, rhinophyma, granulomatous rosacea, acne agminata, tuberculid of Lewandowsky, rosacea fulminans
Contributor Information and Disclosures
Author
Agnieszka Kupiec Banasikowska, MD, Consulting Staff, Division of Dermatology, Georgetown University Medical Center
Agnieszka Kupiec Banasikowska, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Dermatologic Surgery
Disclosure: Nothing to disclose.
Coauthor(s)
Saurabh Singh, MD, Staff Physician, Department of Dermatology, Georgetown University/Washington Hospital Center
Disclosure: Nothing to disclose.
Medical Editor
Franklin Flowers, MD, Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, University of Florida College of Medicine
Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology
Disclosure: Nothing to disclose.
Pharmacy Editor
Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.
Managing Editor
Christen M Mowad, MD, Associate Professor, Department of Dermatology, Geisinger Medical Center
Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Phi Beta Kappa
Disclosure: Nothing to disclose.
CME Editor
Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.
The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Ravi Ratnavel, MD, and Mana Ogholikhan, MD, to the development and writing of this article.
Further ReadingClinical trials
Safety and Efficacy Study of Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel to Treat Rosacea
Efficacy of Topical Azelaic Acid 15% Gel Plus Anti-Inflammatory Dose Doxycycline or Metronidazole Gel 1% Plus Anti-Inflammatory Dose Doxycycline in Moderate Papulopustular Rosacea
Efficacy of Topical Cyclosporin for Ocular Rosacea
ORCA - Oracea® for Rosacea: A Community-Based Assessment
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