Diagnosis and Treatment of Rosacea - PDF Document

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  1. CLINICAL REVIEW Diagnosis and Treatment of Rosacea Aaron F. Cohen, MD, and Jeffrey D. Tiemstra, MD Background: Rosacea is a common skin disorder affecting middle-aged and older adults. Many patients mistakenly assume that early rosacea is normally aging skin and are not aware that effective treatments exist to prevent progression to permanent disfiguring skin changes. Methods: The medical literature was reviewed on the pathophysiology, diagnosis, and treatment of rosacea. MEDLINE was searched using the key search terms “rosacea,” “rhinophyma,” “metronidazole,” “Helicobacter pylori,” and “facial redness.” Results and Conclusions: Rosacea is easily diagnosed by physician observation, and physicians should initiate discussion of rosacea treatment with patients. Effective treatment of rosacea includes avoidance of triggers, topical and oral antibiotic therapy, both topical and oral retinoid therapy, topical vitamin C therapy, and cosmetic surgery. (J Am Board Fam Pract 2002;15:214–7.) As the general population ages and the baby boomers increasingly dominate clinical practice, a frequent complaint is the red face. Of the many causes of the red face, rosacea will be the diagnosis for approximately 13 million Americans.1Although not a life-threatening condition, rosacea produces conspicuous facial redness and blemishes that can have a deep impact on a patient’s self-esteem and quality of life. Rhinophyma, the most prominent feature of advanced rosacea, is often mistakenly associated with alcoholism, as caricatured by W.C. Fields, further stigmatizing rosacea patients. A sur- vey by the National Rosacea Society reported that 75% of rosacea patients felt low self-esteem, 70% felt embarrassment, 69% report frustration, 56% felt that they had been “robbed of pleasure or happiness,” 60% felt the disorder negatively af- fected their professional interactions, and 57% be- lieved that it adversely affected their social lives.2 Much of this suffering is unnecessary, however, because rosacea is a condition that can be easily diagnosed and effectively treated in most patients. ing MEDLINE. Key search terms included “rosa- cea,” “rhinophyma,” “metronidazole,” “Helicobacter pylori,” and “facial redness.” Diagnosis Rosacea develops gradually. Many patients, un- aware that they suffer from a treatable skin condi- tion, assume that the intermittent facial flushing, papules, and pustules are adult acne, sun or wind burn, or normal effects of aging. Correct diagnosis and early treatment of rosacea are important be- cause, if left untreated, rosacea can progress to irreversible disfigurement and vision loss.3Rosacea is a vascular disorder of distinct, predictable symp- toms that follows a remarkably homogenous clini- cal course. Rosacea generally involves the cheeks, nose, chin, and forehead, with a predilection for the nose in men.4 There are four acknowledged general stages of rosacea (Table 1).4Stage I can be described as pre-rosacea. This stage is characterized by frequent blushing, especially in those who have a family history of rosacea. Blushing as a symptom of rosa- cea can start in childhood, although the typical age of onset for rosacea is 30 to 60 years.5There might be increased frequency of facial flushing or com- plaints of burning, redness, and stinging when us- ing common skin care products or antiacne thera- pies. The second stage of rosacea is vascular. At this point in the disease progression, transitory ery- thema of midfacial areas, as well as slight telangi- ectasias, become apparent.4In the third stage of Methods We undertook a literature review on the patho- physiology, diagnosis, and treatment of rosacea us- Submitted, revised 11 October 2001. From Family Physicians of Naperville (AFC, JDT), Fam- ily Practice Residency Department, Provena Health/Saint Joseph Medical Center, Naperville, Ill. Address reprint re- quests to Jeffrey D. Tiemstra, MD, Family Physicians of Naperville, 24024 W Brancaster Dr, Naperville, IL 60564. 214 JABFP May–June 2002 Vol. 15 No. 3

  2. Table 1. Rosacea Staging. Table 2. Brief Differential Diagnosis of Rosacea. Stage Symptoms and Signs Flushing, autonomic mediated Exercise Spicy food Emotions Horner syndrome Rosacea Atopic dermatitis Seborrheic dermatitis Systemic lupus erythematosus Dermatomyositis Acne vulgaris and steroid-induced acne Perioral dermatitis Physical erythema Mechanical Thermal Electromagnetic Contact and photocontact dermatitis Medications Sarcoidosis I Pre-rosacea Frequent blushing Easy irritation and erythema of facial skin Vascular stage Transitory erythema of midfacial areas Early telangiectasias Deeper facial erythema Increased telangiectasias Papule and pustule formation Tissue hyperplasia Rhinophyma Possible ocular inflammation II III IV rosacea, the facial redness becomes deeper and per- manent. Telangiectasias increase, and papules and pustules begin to develop. During this stage, ocular changes, such as conjunctivitis and blepharitis, can develop.6Edema can develop in the region above the nasolabial folds. In the fourth stage, there is continued and increased skin and ocular inflamma- tion. Ocular inflammation can progress to keratitis and result in loss of vision. Multiple telangiectasias can be found in the paranasal region. It is at this point that fibroplasia and sebaceous hyperplasia of the skin produces the nasal enlargement known as rhinophyma.4 Several skin conditions share some clinical fea- tures with rosacea. Acne vulgaris causes come- dones, papules, pustules, and localized inflamma- tory nodules but not the generalized erythema, telangiectasias, and other vascular features of rosa- cea. Seborrheic dermatitis, perioral dermatitis, and the malar rash of lupus can all cause mild erythema, but these conditions will not produce the charac- teristic flushing, telangiectasias, papules, and pus- tules of rosacea.1Sarcoidosis can closely mimic rosacea by producing red papules on the face, but the disease will usually manifest itself in other or- gans as well. In addition, a biopsy will show sarcoid granulomas.7A more complete listing of the differ- ential diagnosis appears in Table 2. Adapted from Murray.8 that atrophy of the papillary dermis provides for easier visualization of the dermal capillaries.9 Edema can develop as a result of the increased blood flow in the superficial vasculature. This edema might contribute to the late-stage fibropla- sia and rhinophyma.1It has been suggested that Helicobacter pylori infection is a cause of rosacea. H pylori, originally implicated as the cause of gastric ulcers, has more recently been associated with ur- ticaria, Henoch-Scho ¨nlein purpura, and Sjo ¨gren syndrome. In a 1999 study, however, Bamford et al10found there was no benefit in the eradication of H pylori compared with placebo in the treatment of rosacea, although both subjects and controls expe- rienced improvement in the rosacea symptoms. Thus the role of H pylori in rosacea remains uncer- tain, and the cause of rosacea remains elusive. Treatment The most important first step in the treatment of rosacea is the avoidance of triggers. Triggers are both exposures and situations that can cause a flare-up of the flushing and skin changes in rosacea. Principal among these is sun exposure. Rosacea patients must be advised always to apply a nonirri- tating facial sun block when outdoors. Stress, through autonomic activation, can also increase the flushing. Alcohol consumption, while not a cause in Pathophysiology Although the exact pathogenesis of rosacea is un- known, the pathologic process is well described. The erythema of rosacea is caused by dilation of the superficial vasculature of the face.1It is thought Rosacea 215

  3. itself, can aggravate this condition through periph- eral vasodilation. Spicy foods can also aggravate the symptoms of rosacea through autonomic stimula- tion. Finally, care must be taken to use only those facial cleansers, lotions, and cosmetics that are non- irritating, hypoallergenic, and noncomedogenic. Rosacea should be treated at its earliest manifes- tations to mitigate progression to the stages of edema and irreversible fibrosis. Antibiotics have traditionally been considered the first line of ther- apy, although their success is considered to be pri- marily due to anti-inflammatory effects rather than antimicrobial ones.4Topical metronidazole, which is effective for stage I and stage II rosacea and avoids the toxicity of systemic treatment, is consid- ered first-line therapy.11Metronidazole is available in a twice-daily application of 0.75% cream or gel and in a newer once-daily 1.0% formulation.4No significant difference in efficacy has been found between the once-daily 1.0% medicine and the twice-daily 0.75% medicine.12Sulfacetamide lotion can also be used in place of metronidazole. In certain patients, sulfacetamide might be less irritat- ing than metronidazole.4 Rosacea responds well to oral antibiotics. Start- ing treatment with simultaneous oral and topical therapy reduces initial prominent symptoms, pre- vents relapse when oral therapy is discontinued, and maintains long-term control.6Oral therapy is generally continued until inflammatory lesions clear or for 12 weeks, whichever comes first.12 Tetracycline is the primary oral antibiotic pre- scribed for rosacea therapy, at a dosage of 1.0 to 1.5 g/d divided into 2 to 4 daily doses. Minocycline at 100 mg two times a day is an acceptable alterna- tive.13Doxycycline is another acceptable alterna- tive, although the monohydrate formulation, in a dosage of 100 mg once daily, is more consistently effective and has fewer gastrointestinal side effects than the hyclate form.13,14Clarithromycin, 250 mg to 500 mg twice daily, has been found to be as effective as doxycycline but with a more benign side effect profile.15 acid with topical metronidazole 0.75% cream for treatment of papulopustular rosacea. Maddin con- cluded that both medicines were equally effective in reducing the number of inflammatory lesions and the associated signs and symptoms of rosacea. When the study physicians’ rating of the overall improvement was considered, however, the azelaic acid was considered to be considerably more effec- tive. The patients involved in the study also pre- ferred the azelaic acid.16 Topical retinoic acid has been shown to have a beneficial effect on the vascular component of ro- sacea.17The drawbacks of retinoic acid therapy include delayed onset of effectiveness, dry skin, erythema, burning, and stinging.17Retinaldehyde is intermediate in the natural metabolism of retin- oids, between retinal and retinoic acid, and is gen- erally well tolerated while retaining most of the therapeutic activity of retinoic acid.17Daily appli- cation of a 0.05% retinaldehyde cream for 6 months was found to yield positive and statistically significant outcomes in 75% of those patients un- dergoing treatment.17Specifically, improvements were found in erythema and telangiectasias, the vascular components of rosacea. Topical vitamin C preparations have recently been studied in the reduction of the erythema of rosacea.18Daily use of an over-the-counter cos- metic 5.0% vitamin C (L-ascorbic acid) prepara- tion was used in an observer-blinded and placebo- controlled study. Nine of the 12 participants experienced both objective and subjective improve- ment in their erythema.18It was suggested that free-radical production might play a role in the inflammatory reaction of rosacea, and that the an- tioxidant effect of L-ascorbic acid might be respon- sible for its effect. These promising preliminary results still need to be confirmed in larger, long- term studies. Treatment of Advanced Disease Recalcitrant rosacea can respond to oral isotreti- noin therapy. In a recent study of 22 patients with mild to moderate rosacea, major reductions in er- ythema, papules, and telangiectasias were noted by the ninth week of treatment.19Isotretinoin reduces the size of sebaceous glands and alters keratiniza- tion. Recalcitrant cases of rosacea have been suc- cessfully treated with 0.5 mg/kg/d of isotretinoin.12 Isotretinoin, of course, has serious side-effects, New Therapies Azelaic acid is a naturally occurring, dicarboxylic acid possessing antibacterial activity. It is available as a 20% cream and is generally used as an alter- native treatment for acne vulgaris. In 1999 Mad- din16compared once-daily applications of azelaic 216 JABFP May–June 2002 Vol. 15 No. 3

  4. 8. Murray AH. Differential diagnosis of a red face. J Cutan Med Surg 1998;2(Suppl 4):11–5. 9. Litt JZ. Rosacea. how to recognize and treat an age-related skin disease. Geriatrics 1997;52:39–40, 42, 45–7. 10. Bamford JT, Tilden R, Blankush J, Gangeness DE. Effect of treatment of Helicobacter pylori infection on rosacea. Arch Dermatol 1999;135:659–63. 11. Breneman DL, Stewart D, Hevia O, Hino PD, Drake LA. A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. Cutis 1998;61:44–7. 12. Thiboutot D. Acne and rosacea. New and emerging therapies. Dermatol Clin 2000;18:63–71. 13. McDonnell JK, Tomecki KJ. Rosacea: an update. Cleve Clin J Med 2000;67:587–90. 14. Bikowski JB. Treatment of rosacea with doxycycline monohydrate. Cutis 2000;66:149–52. 15. Torresani C, Pavesi A, Manara GC. Clarithromycin versus doxycycline in the treatment of rosacea. Int J Dermatol 1997;36:942–6. 16. 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(6 Pt 1):961–5. 17. Vienne MP, Ochando N, Borrel MT, Gall Y, Lauze C, Dupuy P. Retinaldehyde alleviates rosacea. Der- matology 1999;199(Suppl 1):53–6. 18. Carlin RB, Carlin CS. Topical vitamin C prepara- tion reduces erythema of rosacea. Cosmetic Derma- tol 2001;Feb:35–8. 19. Erdogan FG, Yurtsever P, Aksoy D, Eskioglu F. Efficacy of low-dose isotretinoin in patients with treatment-resistant rosacea. Arch Dermatol 1998; 134:884–5. most notably its teratogenic potential. Female pa- tients of childbearing age must be strongly advised to use effective birth control. Stage IV of rosacea, involving irreversible fibrotic changes, such as rhi- nophyma, does not respond well to medical ther- apy. At that point, the patient should be referred for cosmetic surgery, such as cryosurgery and laser therapy. In the aging US population, rosacea is an in- creasingly common disorder. Although rosacea causes only limited physical effects, the prominent visibility of these changes often yields intense psy- chosocial distress. Although the exact cause of ro- sacea is unknown, its progression, signs, and symp- toms can be readily alleviated by the primary care physician. References 1. Zuber TJ. Rosacea: beyond first blush. Hosp Pract (Off Ed) 1997;32:188–9. 2. Coping with rosacea: tips on lifestyle management for rosacea sufferers. Barrington, Ill: National Rosa- cea Society, 1996. 3. Kligman AM. Ocular rosacea. Current concepts and therapy. Arch Dermatol 1997;133:89–90. 4. Zuber TJ. Rosacea. Dermatology. Prim Care 2000; 27:309–18. 5. Habif TP. Clinical dermatology: a color guide to diagnosis and therapy. St Louis: Mosby, 1996:182–3. 6. Bikowski J. The great imitator. Fam Pract Recert 1997;19:61–76. 7. Millikan L. Recognizing rosacea. Postgrad Med 1999;105(2):149–50, 153–8. Rosacea 217