REVIEW

JONELLE K. MCDONNELL, MD KENNETH J. TOMECKI, MD Department of Dermatology, Cleveland Clinic Department of Dermatology, Cleveland Clinic

Rosacea: An update

• ABSTRACT | >1 OSACEA is a chronic and recurrent LAM inflammatory skin disease characterized is a common inflammatory skin disease affecting by erythema, papules, pustules, telangiectasia, the central face of adults. Its etiology is unknown. Early and occasionally sebaceous hyperplasia, which diagnosis and appropriate treatment, usually with topical or primarily affects the central face. The disease systemic antibiotics or both, minimizes symptoms and helps evolves in stages and affects middle-aged to prevent complications. adults. Early diagnosis and thoughtful manage- ment help to control the disease and to mini- • KEY POINTS mize the patient's discomfort and emotional distress. Historically, rosacea has been a mis- Rosacea has a spectrum of cutaneous clinical findings: understood disorder, often attributed to alco- facial erythema, papules, pustules, telangiectasia, and holism and .1 . • INCIDENCE Common triggers are sunlight, stress, exposure to extreme Rosacea is a common and chronic disease that heat or cold, alcohol, hot beverages, and spicy foods. affects approximately 13 million Americans, or about 1 in 20 people. Because rosacea fre- Rosacea can resemble other diseases, including acne, quently affects people of northern European seborrheic dermatitis, systemic lupus erythematosus, and heritage, it is often called the "curse of the sarcoidosis. Celts."2 In contrast, it is rarely seen in dark- skinned individuals.3 In most patients, the Ocular involvement occurs in more than 50% of patients onset occurs between the ages of 30 and 50. with rosacea. The early stages affect women more often than men at a ratio of 3 to 1, but men more often Oral tetracycline and topical metronidazole are the develop disfiguring rhinophyma. mainstays of therapy for rosacea. • PATHOGENESIS

The exact pathogenesis of rosacea is unknown, but it is probably multifactorial. Gastrointestinal disease. A link with gas- trointestinal disease (eg, dyspepsia with gastric hypochlorhydria and Helicobacter pylori infec- tion) is inconclusive with regard to incidence and treatment.4.5 An Italian study4 suggested a causative association between H pylori and rosacea; histologic examination of the stomach mucosa revealed that 26 (84%) of 31 patients with rosacea had H pylori infection, compared with 50% in the general population. Serologic testing in another study5 revealed anti-H pylori antibodies in 12 (27%) of 45 patients with

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 67 • NUMBER 8 AUGUST 2000 587 Downloaded from www.ccjm.org on September 25, 2021. For personal use only. All other uses require permission. ROSACEA MCDONNELL AND TOMECKI

rosacea compared with 15 (35%) of 43 healthy Stage 1 is characterized by persistent ery- controls; the difference was not statistically sig- thema and telangiectasia on the nose, cheeks, nificant. When Bamford et al6 gave patients and glabella, usually coupled with sensitivity with rosacea and H pylori clarithromycin (500 after applying facial cleansers, cosmetics, and mg orally three times daily) and omeprazole sun screens. Ocular may devel- (40 mg daily) or placebo for 14 days in a third op. study, both groups improved, with no statistical Stage 2. Progression to stage 2 may occur difference between the groups. within a year. This stage is characterized by H pylori produces urease, which catalyzes persistent inflammatory papules, pustules, the hydrolysis of urea to C02 and ammonia. edema, erythema, telangiectasia, and, occa- The theory is that the ammonia stimulates the sionally, by prominent facial pores that signify release of various gastric hormones, including fibroplasia. gastrin, which in turn induces flushing, a car- Stage 3. Only a small proportion of dinal symptom of rosacea.1 patients progress to stage 3, characterized by Hypersensitivity to the mite Demodex fol- persistent deep erythema, telangiectasia, liculorum or its products may instigate rosacea, papules, pustules, large inflammatory nodules but the evidence is inconclusive.7 The mites or granulomas, and tissue hyperplasia. Facial inhabit human follicles and sebaceous glands contours become coarse and irregular, and the and induce lymphocytic infiltration that may thickened, edematous skin has a peau d'orange lead to papule or pustule formation. In an texture. Hypertrophy of connective tissue and early study,8 patients treated with 3% sulfur sebaceous glands with increased collagen ointment improved, but the treatment did not deposition leads to disfiguring rhinophyma, affect the Demodex population. more often in men than women, although Vascular and hormonal factors may be three times as many women as men have important. Specifically, migraine headaches early-stage rosacea. (which are common in patients with rosacea) and menopause (with its vasomotor instabili- • OCULAR ROSACEA Patients ty) both support a vascular pathogenesis for experience rosacea. Ocular involvement occurs in more than 50% of patients with rosacea. Symptoms are non- periods of • STAGES specific but include burning, stinging, tearing, remission and and a foreign-body sensation.11 Some patients Patients with rosacea experience periods of experience contact-lens intolerance, photo- relapse remission and relapse. In some, the disease phobia, eye pain, conjunctival injection, and progresses sequentially through stages; in oth- scaly, inflamed eyelids. ers, it does not. Suggested causative factors include a cell- Episodic erythema may precede the first mediated immune response to Demodex follicu- stage in susceptible persons. Such individuals lorum and meibomian gland dysfunction.12 are predisposed to blushing and flushing that Ophthalmic disease develops independently is provoked by nonspecific triggers such as of facial rosacea and may precede it. Flushing ultraviolet radiation, heat, cold, chemical irri- tends to occur with ocular disease. Rosacea tation, strong emotions, alcoholic beverages, keratitis has a poor prognosis and can lead to hot drinks, and spices.9 Iodine injections (used corneal opacity, scarring, and blindness. during x-ray studies) and the use of topical corticosteroids can induce a rosacea flare. • DIFFERENTIAL DIAGNOSIS Eventually, flushing and blushing lead to per- manent erythema on the central part of the The differential diagnosis of rosacea includes face cheeks, nose, chin, and forehead and, acne vulgaris, seborrheic dermatitis, systemic occasionally, on the V-area of the chest. and discoid lupus erythematosus, sarcoidosis, Proposed mediators of this erythema are sub- and systemic flushing disorders. stance P, histamine, serotonin, and Acne vulgaris affects teenagers and young prostaglandins.10 adults. Comedones and are common in

588 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 67 • NUMBER 8 AUGUST 2000 Downloaded from www.ccjm.org on September 25, 2021. For personal use only. All other uses require permission. acne but not in rosacea. Telangiectasia and TABLE 1 persistent erythema are uncommon in acne vulgaris. Rosacea triggers Seborrheic dermatitis affects the face, Weather typically the T-zone (eyebrows and nasal labi- Sun al folds), and may affect the ears, scalp, and Strong winds the middle of the chest. The dermatitis pro- Cold duces erythema and yellow, greasy scales, Humidity often with pruritus. Seborrheic dermatitis may Emotional influences coexist with rosacea. Stress Lupus erythematosus. The malar or "but- Anxiety terfly" rash of lupus erythematosus can mimic Temperature-related factors the background erythema of rosacea, but Saunas papules and pustules are rare with lupus. If the Hot baths distinction is unclear, an antinuclear antibody Simple overheating test and a skin biopsy for histology and direct Excessively warm environments immunofluorescence are warranted. Physical exertion Facial sarcoidosis may resemble granulo- Exercise matous rosacea. A skin biopsy should differen- "Lift and load" jobs tiate the conditions.9 Beverages Carcinoid syndrome is a reasonable con- Alcohol, especially red wine, beer, bourbon, gin, vodka, sideration for patients with a sudden onset of or champagne severe flushing. The diagnostic test for carci- Hot drinks, including hot cider, hot chocolate, coffee, tea noid syndrome is the 24-hour urinary excre- Foods tion of 5-hydroxyindoleacetic acid. Liver Dairy products, including yogurt, sour cream, and some cheeses • TREATMENT Chocolate and vanilla Soy sauce and vinegars Vegetables, including eggplant, tomatoes, spinach, lima and The primary treatment for rosacea is either navy beans, and peas oral antibiotics or topical metronidazole. Fruits, including avocados, bananas, red plums, raisins, figs, Other therapies include topical antibiotics, and citrus fruits isotretinoin, surgical ablation of telangiectasia Hot and spicy foods and rhinophyma, and avoidance of provoca- Skin care products tive "triggers." The goal of therapy is remis- Cosmetics and hair sprays that contain alcohol, witch hazel, sion. or fragrances The papular/pustular component of Topical steroids rosacea responds well to oral antibiotics, Any substance that causes redness or stinging, such as soaps specifically tetracycline (initially 1.0 to 1.5 and astringents g/day, tapered after 1 to 2 months), doxycy- cline (100 mg once or twice daily), or minocycline (100 mg twice a day). Tetracycline and doxycycline are also used but has no effect on telangiectasia or flush- to treat ocular rosacea13; the doses used are ing.1'' Regular use promotes remission. A new the same as for the dermatologic manifesta- 1% formulation of metronidazole (Noritate), tions. The effect of antibiotic therapy in applied once daily, may improve patient com- rosacea is more anti-inflammatory than pliance.15 Topical metronidazole can be used antibacterial. as monotherapy or, in more severe disease, in Topical metronidazole, available as a combination with oral antibiotics. 0.75% aqueous gel, lotion, or cream Isotretinoin (Accutane), 0.5-1.0 (MetroGel/Cream/Lotion), is safe and effec- mg/kg/day for 1 to 3 months, is an alternative tive for moderate-to-severe disease. Applied for patients with severe or resistant rosacea. twice daily, it reduces papules and pustules, Adverse effects include mucosal dryness,

589 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 67 • NUMBER 8 AUGUST 2000 Downloaded from www.ccjm.org on September 25, 2021. For personal use only. All other uses require permission. ROSACEA MCDONNELL AND TOMECKI

myalgias, , and elevated lipids. such, they should discontinue or minimize Because the drug is a known teratogen, female their use of all irritants such as soaps, cleansers patients must practice birth control while tak- that contain alcohol, and astringents. They ing the drug and undergo rigorous follow-up.16 should use a nonirritating, broad-spectrum The package insert recommends using two UVA and UVB sunscreen with a sun protec- birth control methods and undergoing month- tive factor (SPF) of 15. Patients can help con- ly pregnancy tests. Ophthalmic rosacea may trol their symptoms by avoiding triggers (IABLE worsen with isotretinoin therapy. 1). A diary of symptoms may help to identify Rhinophyma and telangiectasia require such triggers. surgical treatment. A CO2 laser can remove For more information on rosacea, con- excess tissue and recontour the nose; the pulse tact the National Rosacea Society al 800 dye laser can eradicate telangiectasia.17'18 South Northwest Highway, Suite 200, Barrington, 1L 60C10; (800) 66-25874 (NO- Other skin care suggestions BLUSH). The organization also has a web- Most rosacea patients have sensitive skin. As site at www.rosacea.org. •

• REFERENCES ing for dry eyes in patients with rosacea. J Am Acad Dermatol 1992; 26:211-214. 1. Millikan L. Recognizing rosacea. Postgrad Med J 1999; 12. Akpek EK, Merchant A, Pinar V, Foster CS. Ocular rosacea: 105:149-158. patient characteristics and follow-up. Ophthalmology 2. Jansen T, Plewig 6. Rosacea: classification and treatment. 1997; 104:1863-1867. J R Soc Med 1997; 90:144-150. 13. Wilkin JK. Use of topical products for maintaining remis- 3. Rosen T, Stone MS. Acne rosacea in blacks. J Am Acad sion in rosacea. Arch Dermatol 1999; 135:79-80. Dermatol 1987; 17:70-73. 14. Bleicher PA, Charles JH, Sober AJ. Topical metronidazole 4. Rebora A, Drago F, Parodi A. May Helicobacter pylori be therapy for rosacea. Arch Dermatol 1987; 123:609-614. important for dermatologists? Dermatology 1995; 15. Jorizzo JL, Lebwohl VI, Tobey RE. The efficacy of metron 191:5-8. idazole 1% cream once daily compared with metronida- 5. Jones M, Knable AL Jr, White MJ, Durning SJ. zole 1% cream twice daily and their vehicles In rosacea: a Helicobacter pylori in rosacea: lack of an association. double blind clinical trial. J Am Acad Dermatol 1998; Arch Dermatol 1998; 134:511. 39:502-504. Patients may 6. Bamford JT, Tilden RL, Blankush JL, Gangeness DE. Effect 16. Plewig G, Nikolowski J, Wolff HH. Action of Isotretinoin of treatment of Helicobacter pylori infection on rosacea. in acne rosacea and gram-negative . J Am Acad help control Arch Dermatol 1999; 135:659-663. Dermatol 1982; 6:766-785. 7. Bonnar E, Eustace P, Powell FC. The Demodex mite popu- 17. Greenbaum SS, Krull EA, Watnick K. Comparison of C02 symptoms by lation in rosacea. J Am Acad Dermatol 1993; 28:443-448. laser and electrosurgery in the treatment of rhinophyma. 8. Robinson TWE. Dermodex folliculorum and rosacea. Arch J Am Acad Dermatol 1988; 18:363-368. avoiding Dermatol 1965; 92:542-544. 18. Polla LL, Tan OT, Garden JM, Parrish JA. Tunable pulsed 9. Thiboutot DM. Acne rosacea. Am Fam Physician 1994; dye laser for the treatment of benign cutaneous vascular triggers 50:1691-1697. ectasia. Dermatologica 1987; 174:11-17. 10. Guarrera M, Parodi A, Cipriani C, Divano C, Rebora A. Flushing in rosacea: a possible mechanism. Arch Dermatol ADDRESS: Jonelle K. McDonnell, MD, Department of Res 1982; 272:311-316. Dermatology, A61, The Cleveland Clinic Foundation, 9500 11. Gudmundsen KJ, O'Donnell BF, Powell FC. Schirmer test- Euclid Avenue, Cleveland, OH 44195.

O CLEVELAND CLINIC CENTER FOR CONTINUING EDUCATION

Downloaded from www.ccjm.org on September 25, 2021. For personal use only. All other uses require permission.