Rosacea: Cause, Triggers and Treatment

From the column editor: Rosacea is a common but little-known disorder of the facial skin that affects an estimated 14 million Americans. In fact, rosacea is becoming increasingly widespread as the baby boomer generation enters the most susceptible ages for its development. Typically, the condition begins any time after the age of 30 and is expressed as redness that may come and go on the cheeks, nose, chin or forehead. The disease is more frequently diagnosed in women; however, more severe symptoms tend to be seen in men that could result from a delay in seeking medical attention until the disorder reaches advanced stages. While the cause of rosacea is unknown and there is no known cure, medical treatments are available to help control the signs and symptoms of this potentially life-disruptive disorder. For example, oral and topical medications may be prescribed to treat the bumps, pimples and redness often associated with the disorder. Dermatologists usually prescribe an initial treatment with oral antibiotics and topical therapy to control the condition more immediately, followed by long-term use of the topical therapy alone to maintain remission. When appropriate, treatments with lasers, intense pulsed light sources or other medical and surgical devices may be used to remove visible blood vessels, reduce extensive redness or correct disfigurement of the nose. Cosmetic dermatology is a growing area and many companies are formulating creams to be used with the medical treatments that patients receive. In addition, the industry is moving toward the development of home devices for personal use. This month, “Tech Edge” welcomes Eric F. Bernstein, MD, who currently serves as clinical associate professor of dermatology at the University of Pennsylvania, to present an overview of rosacea and how it can be treated through laser therapy. Bernstein is a distinguished practitioner, researcher and innovator in the fields of dermatology and laser surgery. He earned his bachelor of science degree from Duke University, medical degree from the Yale University School of Medicine, and materials science and engineering degree in management of technology from the engineering school at the University of Pennsylvania, co-administered by the Wharton School. After fellowships with the National Cancer Institute at the National Institutes of Health and Drexel University, Bernstein joined Jefferson Medical College, where he directed a photobiology laboratory and served as the first director of the laser surgery center. His research on a molecular model of skin photoaging led to the development of his own firm, DakDak LLC, which performs in vitro phototoxicology testing for large pharmaceutical companies and pursues the discovery of novel antiaging and pharmaceutical compounds. Bernstein also sits on the boards of, and consults with, numerous biotechnology and cosmetic firms.

—Mindy Goldstein, PhD

Rosacea is a skin condition characterized by broken (extra) blood vessels on the face, flushing and blushing of facial skin, and by acne-like bumps that occur on the cheeks, nose and chin.1,2These bumps are primarily located around the mouth. In addition, rosacea can affect the eyes, causing irritation that is sometimes severe.3

In searching for the causes of rosacea, experts have identified one hint: rosacea affects predominantly sun-exposed sites.4 Beyond distribution on the face where the sun typically shines, rosacea has been identified as occurring predominantly on the side of an individual’s face nearest the window of their vehicle. For example, in the United States, drivers tend to have more veins on the left side of their face, while passengers have more veins on the right side. Although the glass blocks UVB radiation, it allows 71% of UVA to transmit through.5 Thus, many patients challenged by rosacea exhibit a significant asymmetry of veins on their faces.  

Rosacea affects 5% of the American population, even though a Gallup survey found that 78% of consumers had never heard of rosacea. Another survey by the National Rosacea Society found that 76% of rosacea patients experienced lowered self-esteem due to their rosacea and that 70% of individuals’ work lives were adversely affected; 30% even missed work due to the condition.6 

Various triggers make these vessels acquired through UV exposure fill with blood. Since the face is generally exposed, blood vessels that control the flow of blood to the facial skin more readily respond to various stimuli such as heat and cold. Most consumers have experienced vasoconstriction, or the restriction of blood flow, in the cold when their hands and feet turn whitish or bluish; or alternatively, vasodilatation when their hands become warm and reddened in the heat. 

For individuals with rosacea, various stimuli such as heat, exercise, consumption of wine or other alcohol, sunlight, and a variety of other stimuli cause their very responsive blood vessels in the face to dilate and fill up. Such stimuli can cause a temporary worsening of the symptoms of rosacea but they are not believed to cause the veins to occur. The main exception to the photodistribution of facial veins are veins that commonly occur on the sides of the nose or on the lower cheeks lateral to the mouth. These veins are hereditary and appear independent of sun exposure. 

In addition to linear spider veins and diffuse redness, sun exposure can cause five other types of topical damage: brown spots such as ephiledes and solar lentigos; fine lines and wrinkles; enlarged pores; sagging skin; and skin cancer. An extension of enlarged pores are the sebaceous hyperplasia or overgrown oil glands that appear as small yellow bumps, and the acne-like rash that often accompanies rosacea. Unlike conventional acne that can improve with sun exposure, the acne associated with rosacea often becomes worse with additional sun exposure. 

Sun exposure causes hyperplasia of sebaceous glands, in addition to causing blood vessel growth. 7 Severe hyperplasia of the sebaceous glands on the nose causes rhinophyma, or a thickening of the nose, which can be quite significant.7 

Topical Treatment

Treatment for rosacea begins with prevention. Sunscreen is a must, with reasonable UVB and UVA protection—a minimum of SPF 30 with broad spectrum coverage. The significant asymmetric redness of individuals who spend significant time in the car speaks to the need for UVA protection. In addition, it speaks to the need for window films on vehicles. A UV-blocking window film can block out 99% of UVA; the UVB is blocked by the glass itself. 

In addition to daily sun protection, topical and oral medications can be used to treat rosacea. In most cases these treatments are designed to affect the papular component of rosacea, and not to reduce spider veins.2 Topical metronidazole, for example, is used to treat the papular component of rosacea. It was originally employed because it was believed to act against the demodex mites that live on human skin, but more likely it works through anti-inflammatory mechanisms. 8 Other topical treatments such as sulfur-based drugs and related compounds, as well as azelaic acid, which has antibacterial and antikeratinization effects, also are used. Systemic antibiotics such as the tetracyclines can be prescribed to reduce the papular component of rosacea but may also have an anti-inflammatory effect to reduce flushing and blushing. In addition, beta- and alpha-blockers have been employed in attempts to reduce the flushing and blushing associated with rosacea.2 

Laser Treatment

The only treatment that addresses the root cause of rosacea, i.e., the extra blood vessels themselves, is laser treatment. Lasers that target hemoglobin are among the oldest class of lasers used to treat skin and thus have a long safety record. Pulsed-dye lasers (PDLs) were first outlined in the early 1980s9 to treat port-wine stain birthmarks. Such lasers work by allowing the target, in this case the blood vessels, to take up the laser light for a short period of time—long enough to heat the vessels but not so long as to allow the heat to spread from the vessel to the surrounding skin and create a scar. 

Initial PDLs were developed to deliver 577-nm light at the peak of hemoglobin absorption.10 Paradoxically, this wavelength was absorbed so strongly by hemoglobin that it often failed to penetrate entirely through the target vessel, thus failing to remove the vessel in question. The lasers were adjusted to deliver 585-nm light, which was found to better remove port-wine stains.11,12 

To treat linear facial vessels, rosacea, scars and small spider veins of the legs, an even longer wavelength of light was produced—595 nm.13,14 Most pulsed-dye lasers today emit at 595 nm to better treat the wide range of conditions amenable to PDL treatment: spider veins, facial veins and rosacea; cherry hemangiomas; scars, acne and acne scarring; photodamaged skin; red striae; and most other vascular lesions that can occur on the skin. Clinical observations reveal that side effects from PDL treatments are usually temporary and limited to bruising and hives at the treatment site. 

Earlier-generation PDLs were notorious for producing dark, purple bruises at every impact site (see Figure 1). Newer lasers with longer pulse-durations have enabled removal of linear vessels and diffuse redness with little or no bruising (see Figure 2).

The relatively longer pulse-duration of modern PDLs lasts from thousandths to hundredths of a second and allows the removal of target vessels while not being “seen” by the normal vessels in the skin. The normal skin vessels are too small to be significantly affected by PDL treatment, enabling removal of target vessels without damaging the surrounding skin. In addition to PDLs, long pulse-duration neodymium-doped:yttrium-aluminum-garnet (Nd:YAG) lasers, when coupled with a potassium-titanyl-phosphate (KTP) doubling crystal, emits green, 532-nm light that is also strongly absorbed by hemoglobin. These lasers can remove linear vessels with no bruising, or purpura, and to a lesser extent, treat diffuse redness. KTP lasers have been able to produce pulse-durations of 10-50 ms;15 only relatively recently have PDLs been able to do so, greatly limiting the bruising or purpura that can cause almost one week of downtime for some patients.16,17 

Intense pulsed light sources (IPLs) that attempt to emulate a laser but emit broad spectrum light can also be used to treat vessels and rosacea.18 Unlike a laser that emits a single wavelength, IPLs begin with a flashlamp, as many lasers do; however, instead of turning the flashlamp energy into laser light (a costly endeavor), they use a filter such as a piece of colored plastic to filter the light coming from the flashlamp. This removes much of the shorter wavelengths but significant light and invisible laser radiation is emitted outside of the main absorption peak of hemoglobin. 

Thus, much of the light and energy emitted by IPLs does not do the work of removing blood vessels. Instead, it is emitted as heat and contributes to narrowing the therapeutic window of these devices for treatment of vascular lesions as compared with vascular lesion lasers (532 nm Nd:YAG lasers and PDLs). Although these devices emit light in the region of significant hemoglobin absorption and can thus treat vessels, because they are not lasers emitting entirely in the specific range of hemoglobin absorption, they are not recommended to be used for treating rosacea or vascular lesions.

Generally in this author’s practice, two to four laser treatments are administered at four or more week intervals to treat rosacea. Linear vessels are often treated using a relatively long pulse-duration and diffuse redness is subsequently treated with a shorter pulse duration. Alternatively, a compromise in pulse-duration can be used that somewhat addresses both features of rosacea. Typically, mild to moderate redness and swelling occur after treatment and can last from a few hours to, in most cases, a few days. 

Although newer PDLs result in less purpura or bruising following treatment, the trade-off for this is often more swelling or edema following treatment. The upper cheeks below the eyes are particularly susceptible to swelling and if a large number of linear veins are treated with longer pulse-durations in these areas, significant edema can occur that can persist for a few days. In addition to improvement of redness, PDL treatment of facial skin in rosacea patients also improves to a lesser degree the acneiform papules of rosacea, wrinkles, enlarged pores, oily skin and increased pigmentation present in sun-damaged facial skin.14 

A compression handpiece can be used to expel blood from the skin for treating hyperpigmented macules such as freckles, but this often results in some bruising.14 Since melanin absorbs fairly broadly across many wavelengths, a variety of devices, including the q-switched lasers and IPLs, can also be used to remove epidermal pigmentation. A notable exception to this statement is melasma, that perhaps because it is an inflammatory condition, responds poorly to most laser treatments except in certain individual cases. 

As summer approaches, individuals challenged by rosacea are particularly susceptible to flares due to fun in the sun, margaritas, spicy food, exercise and more. Hopefully those formulators reading this column have gained a better understanding of rosacea and its triggers and can devise treatments to help individuals enjoy the outdoors, with adequate sun protection and a margarita in hand. 

References

1.AM Kligman, A personal critique on the state of knowledge of rosacea, Dermatology 208 191–197 (2004) 

2.JQ Del Rosso; JE Wolf, Jr.; J Leyden; LE Millikan; RB Odom; and A Shalita, The treatment of rosacea, Cutis 73, 34–36 (2004)

3.AM Kligman, Ocular rosacea, current concepts and therapy, Arch Dermatol, 133 89–90 (1997)

4.R Marks, The enigma of rosacea, J Dermatolog Treat 18 (6) 326–328 (2007)

5.EF Bernstein, M Schwartz, R Viehmeyer, MS Arocena, CP Sambuco and SM Ksenzenko, Measurement of protection afforded by UV-absorbing window film using an in vitro model of photodamage, Lasers Surg Med 38 337–42 (2006)

6.www.rosacea.org/rr/1998/spring/article_1.php

7.AM Kligman, Actinic rhinophyma: An old disorder with a new name, Cutis 57 389–392 (1996)

8.A Rebora, The management of rosacea, Am J Clin Dermatol 3(7) 489–496 (2002)

9.RR Anderson and JA Parrish, Selective photothermolysis: Precise microsurgery by selective absorption of pulsed radiation, Science 220 524–527 (1983)

10.OT Tan, K Sherwoood and BA Gilchrest, Treatment of children with port wine stains using the flashlamp-pumped tunable dye laser, N Engl J Med 320 416–421 (1989)

11.BA Reyes and RG Geronemous, Treatment of port-wine stains during childhood with the flashlamp-pumped dye laser, J Am Acad Dermatol 23 1142–1148 (1990)

12.EF Bernstein EF, Efficacy of the 1.5 millisecond pulse-duration, 585 nm pulsed-dye laser for treating port-wine stains, Lasers Surg Med 36 341–346 (2005)

13.EF Bernstein, The new-generation, high-energy, 595 nm, long pulse-duration pulsed-dye laser effectively removes spider veins of the lower extremity, Lasers Surg Med 39 218–24 (2007)

14.EF Bernstein and A Kligman, Rosacea treatment using the new-generation, high-energy, 595 nm, long pulse-duration pulsed-dye laser, Lasers Surg Med 40 233–239 (2008) 

15.EF Bernstein, S Kornbleuth, DB Brown and J Black, Treatment of spider veins using a 10 millisecond pulse-duration frequency-doubled neodymium YAG laser, J Dermatol Surg 25 316–320 (1999)

16.EF Bernstein EF, The new-generation, high-energy, 595 nm, long pulse-duration pulsed-dye laser improves the appearance of photodamaged skin, Lasers Surg Med 39 157–63 (2007)

17.EF Bernstein EF, The new-generation, high-energy, 595 nm, long pulse-duration pulsed-dye laser effectively removes spider veins of the lower extremity, Lasers Surg Med 39 218–24 (2007)

18.CA Schroeter, S Haaf-von Below and HA Neumann, Effective treatment of rosacea using intense pulsed light systems, Dermatol Surg 31 1285–1289 (2005)                 

 

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