Rosacea care: optimizing patient management – Clinical Update
Michelle DiBaise
A chronic acneiform skin condition involving inflammation of the pilosebaceous glands oft he face, rosacea is characterized by episodic flushing in response to various stimuli. To help promote better understanding of the disease, a research–based standard classification system has been developed by the National Rosacea Society.
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Rosacea is a common skin disorder, affecting about 13 million persons in the United States. (1) It generally appears after age 30, with a peak incidence in the fourth and fifth decades. (2-5) It is three times more likely to occur in women than in men and is most common among fair-skinned individuals of northern European or Celtic descent. (2-5) Rosacea is also associated with solar elastosis (sun-damaged skin).
The acneiform lesions of rosacea (papules, pustules, and nodules) typically appear on the central face and rarely on the “V” of the chest, the neck, back, scalp, or extremities. There is a notable absence of comedones. Flushing occurs in response to certain stimuli, including caffeine, alcohol, spicy foods, extremes of temperature, and emotional stress. (2-5) The repetitive cycles of small-vessel dilation and flushing may eventually lead to the development of telangiectases all over the face.
ROSACEA CLASSIFICATION SYSTEM
The National Rosacea Society Expert Committee on the Classification and Staging of Rosacea has developed a standard classification system that divides the disease into four distinct subtypes: erythematotelangiectactic rosacea; papulopustular rosacea; phymatous rosacea; and ocular rosacea (see Figure 1 (6), page 99). Evolution often occurs from one subtype to another. Patients with ocular rosacea may need referral to an ophthalmologist for treatment to lessen the risk of vision loss.
[FIGURE 1 OMITTED]
Granulomatous rosacea is the only variant of rosacea presently recognized by the committee. It is characterized by hard yellow, brown, or red cutaneous papules or nodules that typically appear on the cheeks and may lead to scarring. (6)
Rosacea has a fairly typical presentation and history. However, the practitioner must keep other conditions that have similar symptoms in mind (see Table 1, (2-5) page 100, for the differential diagnosis).
PATHOPHYSIOLOGY
Although there are numerous theories regarding the etiology of rosacea, its exact cause remains unknown. Infectious agents, including Demodex folliculorum mites, the gram-negative bacterium Helicobacter pylori, and gastrointestinal disorders (such as gastric hypochlorhydria and ulcerative colitis) have been implicated as possible causes. (7-13) Citing the twofold to threefold risk of migraines among rosacea patients and its higher incidence among perimenopausal women, some researchers propose that vasomotor lability is involved. (2,5)
MANAGEMENT
Rosacea management is directed toward controlling the acneiform lesions, decreasing flushing episodes and the formation of telangiectases, and preventing rhinophyma.
To limit the development of telangiectases, rosacea patients should reduce their consumption of products that cause flushing, such as caffeine, alcohol, and spicy foods. Use of fluorinated corticosteroids, angiotensin-converting enzyme inhibitors, vasodilators, and/ or simvastatin may also increase rosacea flushing.(5) Complete elimination of all offending agents is usually impossible, however, and patients may still flush in response to extremes of stress and temperature.
Rosacea patients should use sunscreen daily (with a sun protectant factor of at least 15) to protect the skin from chronic ultraviolet A and B exposure. (14) Persons with rosacea tend to be sensitive to topical agents and may experience burning or irritation with their use. Thus, finding an effective, tolerable sunscreen can be difficult and frustrating.
Topical Agents
The most common topical treatment is metronidazole, an antiprotozoal and antibacterial agent. Usually applied twice daily to the affected area, metronidazole preparations are most effective on the acneiform lesions and may reduce some erythema but will not reduce the number of telangiectases. (15,16)
Clindamycin 1% (available in cream, lotion, or gel) and erythromycin 2% are also recommended for rosacea treatment. These can improve the acneiform lesions but have little or no effect on erythema, flushing, or telangiectasia formation. (3) Sodium sulfacetamide 10% lotion, alone or in combination with sulfur 5%, is also reported as beneficial for both rosacea and seborrheic dermatitis. (2) The combination product is available as a facial cleanser. (17)
Topical imidazoles (eg, ketoconazole cream) have also been suggested. These antifungal agents decrease acneiform lesions caused by gram-positive bacteria; they also have some anti-inflammatory effect. (2-5)
Topical retinoids can decrease acneiform lesions and reduce erythema. (2) They can be irritating, however, and may not be tolerable. Azelaic acid has been shown to reduce inflammation of papules and pustules associated with moderate rosacea. (15,18)
Some researchers have suggsted use of antiparasitic medications (eg, lindane, permethrin) to eliminate Demodex mites. (19-21) The treatment regimen is generally once daily for two to five days.
Oral Agents
Demonstrating both antibiotic and anti-inflammatory effects, tetracycline, the oral agent of choice for treating rosacea, decreases the number of acneiform lesions and reduces erythema and flushing. Once good control is achieved, the medication should be tapered to the lowest dose necessary for maintenance. Tetracycline’s adverse effects include gastrointestinal upset, photosensitivity, and interference with the efficacy of oral contraceptives. (22,23) A small percentage of patients experience vertigo with the initial doses of the newer tetracyclines. (2,23) Patients should therefore be counseled to take this medication at night until such symptoms, if they occur, subside.
Long-term use of minocycline, another oral treatment option, has been reported to cause a slate-gray skin discoloration, predominantly of the lower extremities. (2,23) Patients using minocycline should be seen at least two to three times per year and counseled to check their skin and gums every month for possible discoloration. If present, the discoloration will fade when the medication is withdrawn but can take months or years to resolve completely.
Other oral antibiotics with possible benefits include erythromycin and trimethoprim-sulfamethoxazole. Erythromycin, which can cause nausea and vomiting, has little effect on the flushing symptoms of rosacea. Adverse effects of trimethoprim-sulfamethoxazole include a decreased white blood cell count and skin eruptions. Because of the risk of life-threatening adverse reactions (eg, toxic epidermal necrolysis), trimethoprim-sulfamethoxazole should be used only as a last resort. (22)
Isotretinoin may be warranted in phymatous rosacea. (3,4) Because it can exacerbate keratitis and blepharitis, this agent is not recommended for ophthalmic rosacea. Duration of therapy is usually five to six months. Adverse effects of isotretinoin use include dry eyes, nose, and lips; skin fragility; photosensitivity; joint pain; headaches; vision changes; thinning hair; mood swings; and epistaxis. (3,4)
Because of reported cases of neutropenia associated with use of isotretinoin, a complete blood cell count is warranted at baseline and at the end of the first month of therapy. (3,4) The following laboratory studies should be obtained monthly: a hepatic function panel to monitor transaminases, a lipid panel to monitor for triglyceride elevations, and–in women of childbearing age–a serum pregnancy test. (3,4) Because isotretinoin is teratogenic, women of childbearing age should use two forms of birth control during therapy.
Although oral metronidazole has been suggested in the treatment of rosacea, (16) it is not approved by the FDA for this use. Furthermore, it may not be appropriate for long-term therapy because of a risk of developing neuropathy. (24)
Surgical Approaches
Rhinophyma is best treated with various surgical and dermatologic modalities, including laser ablation, dermabrasion, planing with a scalpel or razor, electrocautery, and tissue ablation with a C[O.sub.2] laser. Telangiectasias can be successfully removed by vascular laser of electrocautery. (25,26)
CONCLUSION
Rosacea is a disorder of unknown etiology that is characterized by repetitive flushing in the presence of certain stimuli and papulopustular acne of the central face. It can be controlled but it is marked by a chronic course of remissions and exacerbations. Although the acne component usually responds to either topical or oral treatment, the flushing is slower to respond and may not completely remit. Rosacea patients should be counseled to protect their skin with adequate sunscreen, to reduce or eliminate common triggers, and to avoid emotional stress, whenever possible.
TABLE 1 (2-5)
Differential Diagnosis of Rosacea
Autoimmune disorders Polymorphic light eruption Seborrheic dermatitis Systemic lupus erythematosus Perioral dermatitis Carcinoid syndrome Dermatomyositis
Data extracted from Bikowski. Cutis. 2000 (2); Zuber. Prim Care. 2000 (3); Hirsch and Weinberg. Cutis. 2000 (4); Millikan, Postgrad Med. 1999. (5)
REFERENCES
(1.) National Institute of Arthritis and Musculoskeletal and Skin Diseases. Questions and answers about rosacea. Available at: www.niams.nih.gov/hi/topics/rosacea/rosacea.htm. Accessed January 27, 2004.
(2.) Bikowski JB. Rosacea: a tiered approach to therapy. Cutis. 2000;66 (4 Suppl):3-6.
(3.) Zuber TJ. Rosacea. Prim Care. 2000;27:309-318.
(4.) Hirsch RJ, Weinberg JM. Rosacea 2000. Cutis. 2000;66:125-128.
(5.) Millikan L. Recognizing rosacea. Postgrad Med. 1999;105:149-150,153-158.
(6.) Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46:584-587.
(7.) Utas S, Ozbakir O, Turasan A, Utas C. Helicobacter pylori eradication treatment reduces the severity of rosacea. J Am Acad Dermatol. 1999;40: 433435.
(8.) Thiboutot DM. Acne and rosacea: new and emerging therapies. Dermatol Clin, 2000;18:63-71.
(9.) Pakodi F, Abdel-Salam OM, Debreceni A, Mozsik G. Helicobacter pylori: one bacterium and a broad spectrum of human disease! An overview. J Physiol Paris. 2000;94(2):139-152.
(10.) Bamford JT, Tilden RL, Blankush JL, Gangeness DE: Effect of treatment of Helicobacter pylori infection on rosacea. Arch Dermatol 1999;135: 659-663.
(11.) Roihu T, Kariniemi AL. Demodex mites in acne rosacea. J Cutan Pathol. 1998;25:550-552.
(12.) Jansen T, Plewig G. Fulminating rosacea conglobata (rosacea fulminans) and ulcerative colitis. Br J Dermatol 1997;137:830-831.
(13.) Romiti R, Jansen T, Heldwein W, Plewig G. Rosacea fulminans in a patient with Crohn’s disease: a case report and review of the literature. Acta Derm Venereol. 2000;80:127-129.
(14.) Diffey BL, Tanner PR, Matts PJ, Nash JF. In vitro assessment of the broad-spectrum ultraviolet protection of sunscreen products. J Am Acad Dermatol. 2000;43:1024-1035.
(15.) Maddin S. A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. J Am Acad Dermatol. 1999;40:961-965.
(16.) Bannatyne RM. Metronidazole, its bioactive metabolites and acne. Curr Med Res Opin. 1999;15:298-299.
(17.) Bikowski J, Connolly CS. What’s new in rosacea. Skin Aging. 2000;8(12): 33-37.
(18.) Thiboutot D, Thieroff-Eckerdt R, Graupe K. Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies. J Am Acad Dermatol. 2003;48:836-845.
(19.) Pallotta S, Cianchini G, Martelloni E, et al. Unilateral demodicidosis. Eur J Dermatol. 1998;8:191-192.
(20.) Signore RJ. A pilot study of 5 percent permethrin cream versus 0.75 percent metronidazole gel in acne rosacea. Cutis 1995;56:177-179.
(21.) Forstinger C, Kittler H, Binder M. Treatment of rosacea-like demodicidosis with oral ivermectin and topical permethrin cream. J Am Acad Dermatol. 1999;41:775-777.
(22.) Bikowski JB. Treatment of rosacea with doxycyline monohydrate. Cutis. 2000;66:149-152.
(23.) Del Rosso JQ. Systemic therapy for rosacea: focus on oral antibiotic therapy and safety. Cutis. 2000;66(4 Suppl):7-13.
(24.) Kapoor K, Chandra M, Nag D, et al. Evaluation of metronidazole toxicity: a prospective study. Int J Clin Pharmacol Res. 1999 19:83-88.
(25.) Laugh in SA, Dudley DK. Laser therapy in the management of rosacea. J Cutan Med Surg. 1998;2(Suppl 4):S4-24-29.
(26.) Nelson B, Fuciarelli K. Surgical management of rhinophyma. Cutis. 1998;61:313-316.
F.Y.I.
Sun Worshipers, Beware
Australian researchers may have found another reason to avoid the sun, noting a possible link between sunlight and suicide. In a brief report in the American Journal of Psychiatry, Lambert et al note that, between January 1990 and April 1999, the frequency of suicide in Victoria displayed a clear seasonal pattern, with the number of incidents decreasing during the winter and peaking during the spring and summer months. According to the authors, their findings “raise concerns about a possible link between suicide and bright light exposure.”
Source: Lambert G, Reid C Kaye D, et al. Increased suicide rate in the middle-aged and its association with hours of sunlight. Am J Psychiatry. 2003;160:793-795.
Michelle DiBaise works at the University of Nebraska Medical Center Department of Dermatology. She is also an Assistant Professor in the PA program at the university.
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