"A very rare disorder, carcinoid produces flushing and visible blood vessels that are also common to rosacea," said Dr. Joseph Bikowski, clinical assistant professor of dermatology at The Ohio State University. "However, while they often appear on the face, with carcinoid syndrome these symptoms also may extend over the entire body and be accompanied by other manifestations such as diarrhea, abdominal cramping and swelling of the ankles, legs, hands and arms."

Caused by carcinoid tumors that damage organs, carcinoid syndrome is estimated to occur in only 20 to 40 individuals per one million in the U.S. Individuals with carcinoid syndrome may be at significantly greater risk of death than those with tumors alone because the damage is a consequence of the excessive amounts of potent hormones released into the circulation, rather than the size or spread of the tumors themselves.

"Carcinoid may not always be considered because of its rarity," Dr. Bikowski said. "Anyone who may have signs and symptoms of carcinoid should see their doctor."

Just click on Reader Survey and you will be taken directly to an online survey that is identical to the current printed version. Both online and printed results will be consolidated and reported in subsequent issues of Rosacea Review, both in print and on the website.

The current survey is on rosacea research, allowing you to indicate your preference for future scientific investigation. There's also a place for comments, and ideas for future survey topics are welcome.

The NRS survey of 600 rosacea patients found that nearly 52 percent of the respondents had a relative who also suffered from the condition and that people of some nationalities are more likely than others to develop the disorder.

Of those who said they had a relative with rosacea, most indicated it was an immediate family member. Thirty percent reported their mother has or had rosacea, while 35 percent indicated their father, 28 percent cited a sister and 24 percent named a brother. In some cases more than one family member was indicated.

In addition to family history, the survey found that national ancestry also may be an indication of relative risk for rosacea.

Rosacea has often been called the "Curse of the Celts," and data from the new survey support the theory that it is especially prevalent among the Irish. Thirty-one percent of the respondents reported they had at least one parent of Irish ancestry, while only 11 percent of the U.S. population is of Irish heritage, according to the 2000 U.S. Census figures.

However, those of German and English heritage seem to be highly prone to rosacea as well. Forty-one percent of patients responding to the survey reported they had some German ancestry, compared to 15 percent of the U.S. population, and more than 30 percent reported English ancestry, versus 9 percent reporting English ancestry in the national census.

Other nationalities in which rosacea was present at a higher rate than the ethnicity is represented in the U.S. population include Scandinavian, Scottish, French, Polish, Russian, Lithuanian, Hungarian and Czech.

Although little was known about rosacea years ago, some of the survey respondents could trace the condition back more than one generation. Nearly 16 percent reported one of their grandmothers had rosacea, while 14 percent noted that their grandfather was affected.

The facial disorder may be targeting the next generation as well, since nearly 15 percent of the respondents reported one or more of their children have been diagnosed with rosacea. Many also indicated that an aunt, uncle or cousin had been diagnosed with the condition, too.

Other features in the issue include tips for looking your best in photos, Q&As on oily skin and any links between rosacea and other diseases, a new success story and a new patient survey on rosacea and research.

Patients with rosacea "often complain of increased skin sensitivity and frequently describe a burning sensation," said Dr. Daniela Guzman-Sanchez and colleagues of the Wake Forest University School of Medicine. They noted that although this heightened sensitivity is well recognized in practice, there had been no formal research on the phenomenon.

In their study of 24 individuals, 16 had rosacea, half with subtype 1 (erythematotelangiectatic) rosacea, characterized by redness and flushing, and half with subtype 2 (papulopustular) rosacea, characterized by bumps and pimples. The remaining eight individuals served as a control group without rosacea.

All of the study subjects were exposed to a device that warmed the skin of the cheek beginning at almost 90 degrees Fahrenheit, with a potential high of about 122 degrees. Individuals were asked to rate their perception of burning, and skin blood flow and skin temperature were also measured.

The researches found that individuals with both subtypes of rosacea had a significantly greater sensitivity to heat pain on symptomatic skin, compared to skin without symptoms and to the skin of individuals without rosacea. Moreover, when patients rated pain themselves, there was a significantly greater perception of pain in the subtype 1 group with flushing than in those with subtype 2 rosacea.

Skin blood flow was significantly higher in areas with bumps and pimples than in normal skin, and there was a high correlation between skin temperature and skin blood flow in all three groups.

The researchers pointed out that while 15 of the 16 rosacea patients reported burning, none reported itching, and thus it is possible that the increased skin sensitivity explains the common complaint of burning sensation in rosacea. They noted that, although they found no correlation between blood flow and burning perception, future research on the effect of vasodilators such as alcohol and heat on blood flow and heat pain thresholds may be especially valuable.

Reference
Guzman-Sanchez D, Ishiuji Y, Patel T, Fountain J, Chan YH, Yosipovitch G. Enhanced skin blood flow and sensitivity to noxious heat stimuli in papulopustular rosacea. Journal of the American Academy of Dermatology 2007;57:800-805.

"Although the image of a blushing bride may inspire feelings of warmth and endearment, if the redness persists it can be an early sign of rosacea," said Dr. Richard Odom, professor of dermatology, University of California - San Francisco. "Often the initial signs will come and go, but without proper care and treatment the disorder can grow progressively more persistent and severe, with potentially serious consequences both physically and on people's emotional, social and professional lives."

In NRS surveys of more than 1,200 rosacea patients, 76 percent said rosacea's effect on their personal appearance had lowered their self-confidence and self-esteem; 69 percent felt embarrassed; and 63 percent reported difficulty in establishing new relationships because of the condition. Of those who described their rosacea as severe, 94 percent said it had damaged their self-confidence, and 77 percent reported that it had diminished their outlook on life.

"Public awareness is especially important because the disorder is far more common than many people realize," Dr. Odom said. "Anyone with signs of rosacea should seek medical help and protective measures before it becomes increasingly intrusive on their daily life."

In preliminary study results presented at the NRS research workshop during the Society for Investigative Dermatology annual meeting, researchers found that nearly one in 10 American women had rosacea to some degree, and the rate was 16 percent among Caucasians only. Presented by Dr. Alexa Boer Kimball, director of the clinical unit for research in skin care at Harvard Medical School, the study was based on examination of high-resolution digital photographs of 2,933 women aged 10 to 70 who volunteered from the general population.

She noted that subtype 1 (erythematotelangiectatic) rosacea, characterized by facial redness, affected nearly 15 percent of the Caucasian women, compared to 1.5 percent who had the bumps and pimples of subtype 2 (papulopustular) rosacea.

Although it is often more severe in men, rosacea has been found to occur up to three times more frequently in women and can affect individuals of all ages and ethnic backgrounds. In a recent NRS survey of 1,391 rosacea patients, 44 percent said the disorder first appeared between the ages of 30 and 50, while 39 percent reported that the condition began after age 50 and for 17 percent it developed before age 30.

"The good news is that while rosacea cannot be cured, it can be effectively controlled with medical therapy, lifestyle changes and proper skin care," Dr. Odom said. Individuals with any of the following warning signs of rosacea are urged to see a dermatologist for diagnosis and appropriate treatment:

• Redness on the cheeks, nose, chin or forehead.
• Small visible blood vessels on the face.
• Bumps or pimples on the face.
• Watery or irritated eyes.

Because the underlying causes and other key aspects of rosacea are unknown, the NRS conducts a research grants program to encourage and support greater scientific knowledge of this poorly understood disorder. The society is now funding a growing number of research studies on rosacea that may lead to improvements in its treatment, management and potential cure or prevention.

In a study of skin samples with and without rosacea, Dr. Amal Gomaa and colleagues at Boston University found evidence of angiogenesis in both the blood and lymphatic circulatory systems in skin with rosacea lesions. ^[1]

While the development of visible blood vessels, called telangiectasia, has long been recognized in rosacea, evidence of lymphatic vessel growth has not been previously reported, the researchers said. They also noted that study results suggested lymphatic involvement occurs at the beginning of the disease rather than later in its progress. The lymphatic circulatory system consists of vessels that carry a clear liquid that bathes the tissues of the body and may fight infection.

"Our study may highlight new players in the pathogenesis of rosacea," the researchers said in the article. They pointed out that the lymphatic angiogenesis was not expected as no patient had facial swelling, but that the findings support the long-held belief that the lymphatic system is involved in the process of skin inflammation.

The researchers also noted that increased expression of vascular endothelial growth factor (VEGF), which plays a role in angiogenesis, was found only in rosacea-affected skin samples. Interestingly, the study found no difference in VEGF levels between subtype 1 (erythematotelangiectatic) rosacea, characterized by facial redness, and subtype 2, (papulopustular) rosacea, characterized by bumps and pimples, which suggests that telangiectasia may be present in each.

In another study of affected and unaffected skin, Dr. Kyriaki Aroni and colleagues of the University of Athens studied the potential role of angiogenesis and mast cells in rosacea. ^[2]

"It seems increasingly possible that rosacea pathology is a multifactorial process, which opens up areas of research with regard to potential links between different contributing factors," the researchers said. Mast cells, connective tissue cells that release chemical substances in response to injury or allergic reaction, are known to augment inflammatory processes and occur in increased numbers in conditions associated with angiogenesis.

In their study of 69 rosacea patients, the researchers found that the number of mast cells was significantly higher in skin with rosacea, especially later in the disease, suggesting that the cells may be involved in the longer duration of rosacea. They pointed out that rhinophyma (enlargement of the nose), usually a later manifestation of rosacea, is also characterized by increased numbers of mast cells.

References
1. Gomaa AHA, Yaar M, Eyada MMK, Bhawan J. Lymphangiogenesis and angiogenesis in non-phymatous rosacea. Journal of Cutaneous Pathology 2007;34:748-753.
2. Aroni K, Tsagroni E, Kavantzas N, Patsouris E, Ioannidis E. A study of the pathogenesis of rosacea: how angiogenesis and mast cells may participate in a complex multifactorial process. Archives of Dermatological Research DOI: 10.1007/s00403-007-08162.

The signs and symptoms of ocular rosacea in children may be frequently underdiagnosed or misdiagnosed, the researchers said. They examined the records of 20 children with rosacea from 1½ to 14 years old, and noted that though most had minor ocular involvement, five had more serious eye manifestations that if undetected could lead to severe infection and visual impairment.

Reference
Chamaillard M, Mortemousque B, Boralevi F, Marques da Costa C, Aitali F, Taïeb A, Léauté-Labrèze C. Cutaneous and ocular signs of childhood rosacea. Archives of Dermatology 2008;144:167-171.

Also in the issue are tips on talking with your doctor, Q&As on facial redness and age at diagnosis, a new success story and a new patient survey on rosacea and heredity.

"Although many may assume it's just a sunburn or a temporary case of acne, through greater public awareness more people will seek early diagnosis and appropriate therapy before their rosacea becomes a serious intrusion on their emotional, social and professional lives," said Dr. John Wolf, chairman of dermatology at Baylor College of Medicine.

While rosacea varies from one patient to another, its primary signs may include flushing or transient erythema (redness), persistent erythema, papules (bumps) and pustules (pimples), and telangiectasia (visible blood vessels), according to the NRS standard classification of rosacea, developed by a consensus committee and review panel of 17 experts worldwide. Secondary features may include burning or stinging, plaques (raised patches on the skin), a dry appearance, edema (swelling), ocular manifestations and phymatous changes, in which the skin thickens.

The standard subtypes of rosacea reflect the most common patterns of signs and symptoms, and patients may have characteristics of more than one subtype at the same time. Subtype 1 (erythematotelangiectatic) rosacea is characterized by flushing and persistent redness on the central portion of the face, while subtype 2 (papulopustular) rosacea also features transient papules. Subtype 3 (phymatous) rosacea includes thickening of the skin, irregular nodularities and enlargement, especially of the nose.

Subtype 4 is ocular rosacea, where the eyes may have a watery or bloodshot appearance, the sensation of a foreign body, burning or stinging, dryness, itching, light sensitivity or a host of other signs and symptoms. Styes are a common sign of rosacea-related eye disease, and in severe cases vision may be reduced due to corneal complications.

In an NRS survey of 603 patients, 76 percent said rosacea's effect on their personal appearance had lowered their self-confidence and self-esteem, and nearly half said it had diminished their outlook on life. Moreover, for those who described their condition as severe, 94 percent said it had damaged their self-confidence and 77 percent said their rosacea had negatively affected their outlook. Nearly 40 percent said they had canceled business meetings or social engagements because of rosacea's effect on their appearance, and nearly 30 percent had even missed work because of their condition.

The good news is that 80 percent of the survey respondents reported that effective medical therapy had also improved their emotional well-being.

During Rosacea Awareness Month, extensive public education activities will be conducted by the NRS to increase awareness and understanding of this widespread disorder, emphasizing its warning signs and urging those who suspect they may have the condition to see a dermatologist or other physician. In addition, bulk quantities of NRS educational materials are available to health professionals for their patients.

Many women report more flushing episodes and increased numbers of bumps and pimples during these times, according to Dr. Wilma Bergfeld, head of the clinical research section of the dermatology department at Cleveland Clinic and former president of the American Academy of Dermatology.

"There is no research regarding hormones and their effect on rosacea," Dr. Bergfeld said. "However, it has been widely observed that rosacea is often aggravated at menopause and sometimes during mid-cycle." She noted that by treating the underlying hormonal fluctuations, the physician may in effect be treating the rosacea as well.

Hot flashes, for example, commonly trigger flushing in women going through menopause. Dr. Bergfeld said gynecologists now have a number of options for treating this condition, including hormone replacement therapy, and that she also often prescribes antihistamines.

"Using an antihistamine may be very helpful because it is basically an anti-inflammatory medication," she said. "If you can reduce the beginnings of the flush, you can reduce its severity."

She added that antidepressants may be used to treat the emotional effects of menopause, which in turn may reduce the potential for stress-induced rosacea flare-ups.

Women who experience rosacea flare-ups from emotional stress associated with premenstrual syndrome (PMS) may also benefit from medical therapy, according to Dr. Bergfeld. "During the third week of the cycle, estrogen plummets," she explained, noting that patients are usually referred to a gynecologist for treatment of this condition. "For some cases low-estrogen birth control pills may be prescribed to help flatten out the hormonal levels."

Patients may also be advised to chart their symptoms on a calendar and use a diuretic the week before they normally would see the onset of premenstrual symptoms.

Pregnancy poses a more difficult dilemma for doctors treating rosacea because "so many medications are off limits," Dr. Bergfeld said. Often, she will recommend that the patient use an antidandruff shampoo containing zinc as a face wash once or twice a week, because the zinc acts as both an anti-inflammatory and antimicrobial agent but does not penetrate the skin barrier.

Studies have found that rosacea is diagnosed three times as often in women, although it is often more severe in men. Dr. Bergfeld said there may be a variety of reasons why more women seek treatment. She noted that women may be more concerned about their facial appearance, while mild cases of rosacea may not be as noticeable in men. "A dark beard can hide a multitude of things," she said.

"We are delighted that this important program is resulting in significant new findings, and encourage new investigators to submit proposals that may lead to further contributions toward the understanding and more effective management of this widespread disorder," said Dr. Jonathan Wilkin, chairman of the NRS medical advisory board, which reviews and selects grant applications for funding. "We are also grateful for the growing thousands of rosacea patients whose donations make this program possible."

Dr. Richard Gallo, chief of the division of dermatology at the University of California - San Diego, and Dr. Kenshi Yamasaki of the Veterans Medical Research Foundation were awarded $25,000 to continue their NRS-funded research of how cathelicidins may play a role in the development of subtype 2 (papulopustular) rosacea.

In previous study results recently published in Nature Medicine, the researchers found that people with subtype 2 rosacea had abnormally high levels of anti-microbial peptides called cathelicidins, as well as an overproduction of anti-inflammatory peptides known as stratum corneum tryptic enzymes (SCTE). They also discovered that the high level of SCTE results in a different form of cathelicidin than found in patients without rosacea.

By putting these two observations together, the researchers were able to induce signs of rosacea in the skin of mice, thus suggesting that these molecules play an important role in the papules (bumps) and pustules (pimples) associated with subtype 2 rosacea.

In the new study, they will examine these and related substances at the molecular level and conduct further tests in animal models. They note that successful results will further support the hypothesis that high levels and an abnormal form of cathelicidin lead to rosacea, opening the way for new therapeutic approaches.

Dr. Yolanda Helfrich, assistant professor of dermatology at the University of Michigan, was awarded $25,000 to compare subtype 1 (erythematotelangiectatic) rosacea and photoaging, both of which may include the development of telangiectasia (visible blood vessels) and erythema (redness). The study will examine the potential differences and similarities of those signs in respective patient groups at a clinical and molecular level, which may increase understanding of the pathogenesis of rosacea as well as lead to improvements in differential diagnosis and treatment.

Dr. Richard Granstein, chairman of dermatology at Cornell University, and colleagues were awarded $25,000 to continue their research on the role of adenosine triphosphate (ATP) in recruiting inflammatory cells in subtype 2 rosacea. Researchers have found that stress, a common rosacea trigger, may activate the sympathetic nervous system with release of ATP from sympathetic nerves innervating cutaneous blood vessels. Earlier NRS-funded studies had shown that ATP initiates an inflammatory response mediated by human dermal endothelial cells. The researchers will also expand their study to examine whether three other agents produced by nerves elicit effects similar to ATP, and will test whether therapeutic agents for rosacea work by inhibiting the expression of inflammation-causing molecules by endothelial cells.

Dr. Martin Steinhoff, department of dermatology, University of Muenster, Germany, was awarded $25,000 to study the role of neuroimmune interactions in the pathophysiology of rosacea. In an article recently published in the Proceedings of the National Academy of Sciences, Dr. Steinhoff and co-workers revealed a new mechanism by which peptidases regulate the cell signaling of neuropeptide receptors, resulting in the control of neurogenic inflammation. In the new study, by molecular, cellular and genomic approaches, the researchers will attempt to characterize the molecules and receptors involved in the abnormal interaction between neuropeptide receptors and neuropeptide-degrading enzymes, which results in dysregulation and contributes to the development of rosacea.

Researchers interested in applying for grants can obtain forms and instructions by contacting the National Rosacea Society, 800 South Northwest Highway, Suite 200, Barrington, Illinois 60010, telephone 1-888-662-5874, email rosaceas@aol.com or by visiting the Research Grants section of rosacea.org. The deadline for submitting proposals for research grants in 2008 is October 15.

Members of the NRS medical advisory board include Dr. Jonathan Wilkin, former director of dermatologic and dental drug products for the U.S. Food and Drug Administration; Dr. Mark Dahl, chairman of dermatology at the Mayo Clinic-Scottsdale and former American Academy of Dermatology (AAD) president; Dr. Michael Detmar, associate professor of dermatology at Harvard Medical School; Dr. Lynn Drake, Harvard Medical School and former AAD president; Dr. David Norris, chairman of dermatology at the University of Colorado and former president of the Society for Investigative Dermatology; Dr. Frank Powell, consultant dermatologist with the Regional Centre of Dermatology, Dublin, Ireland; Dr. Richard Odom, professor of dermatology at the University of California - San Francisco and former AAD president; Dr. Bryan Sires, clinical associate professor of ophthalmology at the University of Washington; and Dr. Diane Thiboutot, professor of dermatology, Pennsylvania State University.

Also in the issue are tips on coping with rosacea during the holidays, Q&As on tanning beds and caffeine, a new success story and a new patient survey on rosacea and health professionals.