Other topical therapies used to treat rosacea

In mild to moderate papulopustulr rosacea, 10% sodium sulfacetamide and 5% sulfur cream or lotion are effective topical therapies of papulopustular rosacea and can be used to treat concomitant seborrheic dermatitis. It should be avoided in patients with sensitivity to sulfur or sulphonamides. Tinted and sunscreen containing preparations of these products are available, which appeal to some patients.
The choice among these topical agents can be difficult. There is individual variations in patients tolerance and response to treatment (what works for one patient may not always suit another). Most patients usually start with a metronidazole cream or azelaic acid gel applied twice daily.
Occasionally the response will be disappointing and this requires the physician to switch from one topical therapy to another to achieve optimal results. Patients are
adviced that initial prescription is likely to be successful, but that a follow-up
visit is required after three weeks to ensure that they have had a good response.
It is advisable that the physician becomes familiar with the tolerability of two or three topical agents on dry, normal, sensitive and oily skin as well as in patients with various skin types. With experience the clinician will be able to select the appopriate treatment to suit an individual patient.
Other topical therapy used to treat papulopustular rosacea includes, erythromycin 2% solution applied twice daily. This may be slightly drying and irritant and is probably not as effective as the other topical treatments but has the advantage that it can be used safely in the pregnant patient. Tretinoin 0.025% cream or lotion or 0.01% gel applied at night has the theoretical advantage of treating both the actinic damage as well as the rosacea, but is poorly tolerated by rosacea patients with dry sensitive skin and should be avoided in pregnancy. Isotretinoin 0.05% and erythromycin 2% alcohol gel applied as a thin film twice daily may also be effective, but again irritancy may reduce its acceptability to patients and it does not appear to have any advantage over the better tolerated metronidazole and azelaic acid products. Other topical therapies that have been reported to be effective in treating individual or small groups of patients with papulopustular rosacea include various sulfur containing products (often in combination with salicylic acid or precipitated sulfur with 0.75% hydrocortisone lotion), benzoyl peroxide gel (which is quite drying and poorly tolerated on the rosacea patient’s skin) sometimes used in combination with clindamycin 1% or erythromycin, and topical antimite preparations (Permethrin 1% or ivermectin 1.87% creams). There is insufficient
evidence to recommend these medications and the clinician is best advised to adhere to the FDA apapulopustular rosaceaoved and appropriately tested products. Only in the exceptional case will it be necessary to resort to any of these latter agents. Topical calcineurin antagonists such as tacrolimus and pimecrolimus initially showed promise in the treatment of papulopustular rosacea,but they may induce a rosaceiform eruption and so their use for these patients should probably be avoided. The method of application of topical therapies and how they should be used in relation to cosmetic and sun-block creams should be explained to the patient.

Local Treatments for Rosacea

Topical Treatments for Papulopustular Rosacea

Mild to moderate Papulopustular Rosacea will respond well to topical therapy. There is a wide range of topical measures used to treat Papulopustular Rosacea. The most frequently used are the various preparations of metronidazole (creams, gels and lotions which may be available in different strengths) and azelaic acid gel. Azelaic acid gel (15%) and the metronidazole preparations are effective treatments when applied twice daily to the skin. Both of these preparations should be applied to the area of skin affected and not solely to inflammatory lesions. An occasional patient will experience an initial burning sensation with azelaic acid, but this usually settles with continued use. When the rosacea clears, treatment should be continued to maintain remission. If the skin remains in remission over several months, the patient can gradually discontinue treatment, initially applying the preparation once daily for two weeks and then on alternate days for two weeks before stopping.
If a flare occurs, the patient should reintroduce therapy at the original frequency themselves. In this way, the individual can take over the management of their skin condition with occasional supervision by the physician. Metronidazole 0.75% cream preparation is particularly well tolerated by patients with sensitive skin. In comparative studies it would appear that there is little difference in the efficacy of these products (azelaic acid and metronidazole) and that both are well tolerated. They are particularly effective in clearing the inflammatory lesions of Papulopustular Rosacea. The erythema may respond better to the azelaic acid preparation, but can be expected to diminish progressively (over several months) following sucessful with either treatment. Topical metronidazole products should not be prescribed to pregnant or lactating females. Experience with the use of azelaic acid by pregnant mothers is too limited to permit assessment of the safety of its used during pregnancy.

The Best Treatment for Acne Rosacea Can Be A Personal Dilemma

The Best Treatment for Acne Rosacea Can Be A Personal Dilemma

Trying to determine which of the many rosacea products is the best rosacea treatment can be confusing, to say the least. The reason being is that it is generally different for each person due to the variability of the symptoms from individual to individual. Acne rosacea can prove very difficult to treat, however with a proper treatment plan, the condition can be controlled. Though self treatment is not uncommon we generally suggest that you schedule an appointment with a dermatologist to help in developing a rosacea treatment based on your particular set of symptoms.

Rosacea Is Socially Disruptive

Based on surveys conducted with acne rosacea sufferers with more severe symptoms, about 70% of those surveyed claimed that the skin disease had negatively affected their professional and occupational relationships. Also of interest was the fact that 30% stated they had called into work sick to avoid the embarrassment of their rosacea symptoms. It is obvious that this skin affliction not only affects the personal lives of many its sufferers, but also impacts workplace productivity.

Finding the Best Rosacea Treatments

The good news is that you do have options in the treatment of your acne rosacea. The pharmaceutical approach to rosacea control is available through your dermatologist and local pharmacy. The bad news is that this kind of treatment can be irritating at times, especially for those acne rosacea sufferers who are sensitive to antibiotics.

An alternative rosacea treatment to the pharmaceutical approach is available and may better suit your skin condition and particular symptoms. Using a rosacea best treatment alternative is a personal choice that most rosacea patients have pondered. If a natural rosacea treatment sounds preferable to you, there are some very effective new herbal rosacea remedies that can actually relieve your rosacea symptoms. Their secret is a precise combination of herbal ingredients and pure, natural ingredients.

Simply stated, the best rosacea treatment will depend on your particular symptoms and those factors that aggravate your skin condition. Once these conditions become obvious to you, a simple modification to your lifestyle or environment can have a dramatic effect on the frequency and severity of your rosacea flareups. Combine these modifications with a regular skin care program of natural cleansers and moisturizers, and you will have done everything possible to manage your skin condition.

Hope for rosacea: Cytokinin treatment offers patients a new therapeutic option

Hope for rosacea: Cytokinin treatment offers patients a new therapeutic option
By Ilya Petrou, M.D
National report — Several treatment approaches are used for the treatment of rosacea, however no current therapy is considered a panacea for all the symptoms associated with this condition. A recent trial with Pyratine-XR proves to be very effective in treating many of the associated symptoms seen in rosacea, and offers patients a new therapeutic option for this cosmetic thorn.

Pyratine-6 (0.1 percent furfuryl tetrahydropyranyladenine) and pyratine-XR (0.125 percent furfuryl tetrahydropyranyladenine) are second-generation compounds associated with a molecule called kinetin, which have been shown to have a significant therapeutic effect in rosacea. These cytokinin compounds are antioxidants, which positively impact many aspects of skin aging by increasing mitochondrial activity, helping actin and fibroblast function as well as helping in the removal of cellular debris. In the wake of initial therapeutic clinical trial success with pyratine-6 lotion for the treatment of rosacea, Senetek recently completed a clinical study with pyratine-XR lotion in rosacea patients.

In the 48-week study conducted at the University of California, Irvine, 18 patients with mild-to-moderate rosacea received a twice a day treatment with Pyratine-XR lotion. The investigators evaluated inflammatory papule and pustule lesion count, severity of facial erythema and telangiectasias, and participants self-assessed their signs and symptoms of rosacea as well as skin tolerance to the treatment.

Results showed that at 48 weeks, 80 percent of the patients showed an overall clinical improvement including reduction of facial erythema and inflammatory lesions. There was a 90 percent improvement of inflammatory lesions, a 45 percent improvement of erythema and a 28 percent improvement of telangiectasias. In addition, a significant improvement of the skin barrier function from week four through the end of the study was seen, as measured by a decrease in water loss from the skin.

Pyratine-6 was initially studied for photodamage and results showed that in addition to improving fine lines and wrinkles, it also dramatically helped improve erythema. Pyratine-XR is a reformulation of the original compound that appears to be extremely effective in treating the clinical symptoms seen in rosacea, including erythema, inflammatory lesions as well as spider veins.

"Pyratine-XR appears not only to be effective in treating rosacea, but may also be effective for other dermatoses where erythema plays a major role in the symptomatology such as facial redness, inflammatory lesions, telangiectasias, eczema and atopic dermatitis," says Mark Nestor M.D., Ph.D., voluntary associate professor, department of dermatology and cutaneous surgery, University of Miami Miller School of Medicine, Miami.

The three clinical presentations of rosacea include papulopustular, telangiectatic and sebaceous (rhinophyma) type rosacea and all three variants have been amenable to some degree with different treatment approaches. Current treatments for papulopustular type rosacea include oral and topical antibiotics as well as topical metronidazole and azeleic acid, whereas telangiectatic rosacea responds best to laser or IPL therapies. Because rosacea is a chronic condition, therapeutic regimens used are geared for the long-term. According to Dr. Nestor, long-term tolerability and the development of antibiotic resistance, which can be associated with oral and topical antibiotic regimens, are a non-issue with the cytokinin therapy, and is considered one of the major advantages of this novel therapeutic approach.

"The currently used pharmaceutical therapies do not effectively address the erythema associated with rosacea and none of them treat the telangiectasias. Therefore, it is refreshing to have a compound now that can compliment laser or IPL therapy, does not have any side effects and makes the skin look better and at the same time not only decreases the erythema, but also the suppresses exacerbations of rosacea," Dr. Nestor tells Dermatology Times.

Patients in the trial tolerated Pyratine-XR very well and the cosmetic acceptability was very high. The regimen is twice a day with the lotion until improvements are seen which can be as soon as two weeks of therapy. According to Dr. Nestor, any kind of topical therapy, ultimately, has the potential to cause some degree of irritation, but in the trial patients, there was no difference seen here between Pyratine-XR and the vehicle. Pyratine-XR can be used either alone or as an adjunct in patients with rosacea.

"This gives us another option to help us treat our rosacea patients. In addition, Pyratine-XR lotion also seems to improve other aspects of aging skin such as fine lines, roughness and hyperpigmentations," Dr. Nestor says. DT

Disclosure: Dr. Nestor reoports no relevant financial interests.

Pathogenesis of rosacea: Breakthroughs hold promise for therapeutic developments

Pathogenesis of rosacea: Breakthroughs hold promise for therapeutic developments
By Cheryl Guttman

San Diego — Understanding the pathogenesis of rosacea has been advanced by recent research and is expected to provide an important foundation for developing novel, rational approaches to therapy in the future, says Richard L. Gallo, M.D., Ph.D., professor and chief, division of dermatology, University of California, San Diego.

Dr. Gallo discusses findings from a series of research studies that show there is a dysfunction in antimicrobial peptide production and processing in rosacea and that it can arise via multiple pathways.

"This information indicates no one gene or stimulus can explain rosacea in all patients, and therefore, it is consistent with our longstanding frustration in trying to identify a solitary etiologic trigger,

" Dr. Gallo says.

Skin’s immune system

"Now, understanding of these antimicrobial peptides as a critical element of rosacea should offer us new targets of therapy," Dr. Gallo tells Dermatology Times.

Dr. Gallo and colleagues approached their investigations of rosacea pathogenesis from a biochemical and genetic standpoint, considering the key elements of the biology of the disease and their understanding of the functioning of the innate immune system of the skin.

Based on this knowledge, they hypothesized that rosacea reflects an abnormality in the reaction of the early response system to the variety of elements that have been identified as rosacea triggers.

More specifically, they hypothesized that elements of the antimicrobial peptide system and enzymes controlling that system may represent a "choke point" in the communication between the multiple different disease stimuli and the various clinical subtypes of rosacea.

Immunohistochemistry

A series of studies were designed to construct proof for this hypothesis. The first investigated levels of cathelicidin antimicrobial peptides in facial skin and showed significantly higher expression in patients with rosacea compared with unaffected controls as measured by immunohistochemistry, Enzyme-Linked ImmunoSorbent Assay (ELISA) and gene expression. Evaluation with mass spectroscopy showed the size of the cathelicidin peptides was also abnormal in the skin of all rosacea patients compared with controls, indicating a difference in proteolytic processing.

"The differences between rosacea patients and our control samples — uninvolved edges of basal cell carcinoma excisions — were dramatic, and the findings were somewhat surprising to us.

"However, it was the difference in peptide size that really led us to believe we had come upon something important," Dr. Gallo says.

Consistent with that belief, the researchers also found that all rosacea patients had abnormally increased activity of the serine protease enzymes responsible for cathelicidin peptide processing.

In previous research, Dr. Gallo and colleagues had already identified the genes for individual cathelicidin-processing enzymes. Based on that information, they evaluated the expression of the gene for stratum corneum tryptic enzyme (SCTE, kallikrein 5) in facial skin of rosacea patients and found it was also elevated and specifically in areas where the processed cathelicidin peptides were found.

Further experiments aimed to establish significance for the laboratory findings by demonstrating a cause and effect relationship. Applying Koch’s postulates, these experiments investigated the hypothesis that if the unique peptides found only in rosacea skin were important in disease pathogenesis, they could induce findings consistent with the clinical presentation of rosacea.

Cathelicidin peptides

A first in vitro experiment showed that production of pro-inflammatory cytokines by cultured keratinocytes was significantly greater when the skin cells were co-incubated with processed cathelicidin peptides found in rosacea skin compared with peptides from normal skin.

"Although supportive, this finding was not overly convincing. The results of a second experiment blew us away," Dr. Gallo says.

The latter research involved a murine model and evaluated the responses to dorsal skin injections of physiologically relevant concentrations of peptides from normal and rosacea skin.

After just two days of twice daily treatment, the animals injected with the rosacea-related peptides developed a phenotype that reproduced rosacea with the presence of inflammation, a vascular response, and ectasia.Adding strength to the cause and effect relationship was the observation of a dose-related response.

The research has now entered a new phase where studies are evaluating potential correlations between the proposed pathogenic pathway and both gene abnormalities and effective treatments.

These are our last questions, but really represent the beginning of our research project, not the end," Dr. Gallo says.

Available evidence is still limited, but so far, it is entirely consistent with the existing hypothesis. One line of support is derived from an "experiment of nature," which is the finding that a polymorphism of the vitamin D receptor gene leading to excessive production of processed cathelicidin peptides is associated with rosacea fulminans.

Isotretinoin

In addition, it is also known that isotretinoin, which has been found to have beneficial effects in rosacea, influences genes involved in the cathelicidin and SCTE expression system.

Findings from a study examining serine protease levels in facial skin of rosacea patients after they start, stop, and restart minocycline therapy are preliminary but so far are providing a dramatic demonstration of how tetracyclines can affect this innate immune response pathway.

Dr. Gallo says that marked decreases in SCTE levels have been observed after the initiation of minocycline therapy and occur in parallel with improvement in clinical disease activity.

Subsequent minocycline withdrawal and re-initiation corresponded to increases and decreases, respectively, in enzyme activity.

"The effects of minocycline withdrawal and rechallenge on SCTE show the initially observed change with minocycline initiation was not a coincidence and suggest that indeed, tetracycline affects the enzymes that we hypothesize are involved in the pathogenesis of rosacea," Dr. Gallo says. DT

Disclosure: The research has been supported in part by a seed grant from the National Rosacea Society.

Rosacea diagnosis

The diagnosis of Acne rosacea is made by fulfilling one of several primary and one of many secondary criteria. Primary criteria for Acne rosacea include transient erythema/flushing, persistent facial redness, papules and pustules, and increased facial telangiectasias. Secondary criteria include burning/stinging, elevated red facial plaques with or without scale, dry/scaly skin, persistent facial edema (subtypes of solid facial or soft facial type), phymatous changes, and ocular manifestations such as burning/itching, conjunctival hyperemia, lid inflammation, styes, chalazia, and corneal damage.
There are four subtypes and one variant of Acne rosacea that have been defined by the National rosacea Society committee on the classification and staging of Acne rosacea: (i) erythematotelangiectatic, (ii) papulopustular, (iii) phymatous, and (iv) ocular. Erythematotelangiectatic rosacea is characterized by flushing and persistent central facial erythema with or without telangiectasia. The papulopustular type has persistent central facial edema and transient papules, pustules, or both. Phymatous rosacea occurs most often on the nose (rhinophyma) and is characterized by thick skin with an irregular surface, nodularities, and bulbous enlargement. Careful evaluation of a nose with the changes of rhinophyma should be undertaken because basal cell carcinomas may be present, as well as less common tumors. Lastly, the ocular type of rosacea has many symptoms, of eye affection. Granulomatous rosacea is a variant characterized by noninflammatory, hard, brown, yellow, or red papules/nodules of the central face. It is of note that rosacea fulminans (pyoderma faciale), steroid-induced acneiform eruption, and perioral dermatitis are not considered Acne rosacea variants but separate entities.
Ocular changes (blepharitis, conjunctivitis, and keratitis) and sebaceous hyperplasia of the nose (rhinophyma) may be associated with ocular rosacea. Differential diagnostic considerations include (i) acne vulgaris, which is characterized by a wider distribution of lesions and the presence of comedones, (ii) periorificial dermatitis, (iii) seborrheic dermatitis, (iv) malignant carcinoid syndrome, (v) lupus erythematosus, and (vi) photodermatoses. Ocular rosacea has been theorized to be secondary to increased local levels of interferon-1 that is pro-inflammatory and leads to lid irritation and erythema. Lipid breakdown in the tears releases fatty acids that are also irritating. Some studies have also shown a more alkaline pH of tears in patients with Acne rosacea.

Acne rosacea causes

Acne rosacea is a chronic disorder of unknown cause that affects the central face. At least 13 million people are affected by this noncurable disorder. It is characterized by two clinical components: a vascular change consisting of intermittent or persistent erythema and flushing and an acneiform eruption with papules, pustules, cysts, and sebaceous hyperplasia. There is no correlation between the sebum excretion rate and the severity of Acne rosacea. Lesional blood flow as measured by laser Doppler is three to four times that of controls. Onset is most often between the ages of 30 and 50; pediatric cases have also been reported. Although women are affected three times as frequently as men, the disease may become more severe in men. Acne rosacea is much more common in light-skinned, fair-complexioned individuals but may also occur in darker skin types. It is estimated that 10% of individuals in Sweden have Acne rosacea.
There is speculation that a defect in the trigeminal afferent nerve pathway contributes to a predisposition to facial flushing. Over time, after repeated bouts of flushing, the vessels become ectatic and there is permanent vasodilatation. Hot liquids are thought to promote erythema and flushing when they heat up the tissues of the oral mucosa, leading to a countercurrent heat exchange with the carotid artery. A further signal from the carotid body is then relayed to the hypothalamus (the body's thermostat), which signals the body to dissipate heat through flushing and vasodilatation because of the perceived increase in core body temperature.
Helicobacter pylori, a microaerophilic gram-negative bacteria implicated in gastric ulcer disease, has been theorized to be the inciting organism in Acne rosacea on the basis of an increased incidence of dyspepsia in this population and the responsiveness of Acne rosacea to metronidazole. Fifty percent of the world's population and 25% of the US population may have antibodies to this organism. Colonization is associated with increased levels of serum gastrin, which can cause flushing. Also, H. pylori infection can increase levels of histamine, prostaglandins, leukotrienes, and various other cytokines. Therapy to eradicate this organism usually consists of a combination of oral metronidazole, amoxicillin, and omeprazole. Conflicting studies regarding this association with Acne rosacea have recently been in the literature. In general, it is felt that strong support for a link between H. pylori infection and Acne rosacea is lacking. Large case control studies would be needed to prove this association because of the high baseline incidence of this exposure.
Infection with Demodex mites is common, with infection approaching 100% in sensitive tests of healthy adults. Some have hypothesized that infection with Demodex is a cause of Acne rosacea. There is controversy within the literature whether this is the case. In one study, there was a link between higher mite counts and papulopustular but not erythematotelangiectatic Acne rosacea. It is unclear whether Demodex is pathologic or just normal skin flora.