For rosacea sufferers, treatment arsenal continues to grow

 “We don’t yet know the cause of rosacea. And just as predisposing factors can account for worse-than-average cases of acne, different patients probably have different causes of rosacea,” says Dr. Webster, clinical professor of dermatology, Jefferson Medical College, Philadelphia, and past-president of the American Acne and Rosacea Society. He spoke at the 70th annual meeting of the American Academy of Dermatology.

New topicals coming

Among topical treatments, the only agents approved for rosacea are metronidazole and azelaic acid. Dr. Webster says, however, that benzoyl peroxide/clindamycin also may prove useful (Breneman D, Savin R, VandePol C, et al. Int J Dermatol. 2004;43(5):381-387).

“It’s hard to know how this is working, since Propionibacterium acnes doesn’t seem to play a role in rosacea,” he says. As in acne, he speculates, benzoyl peroxide/clindamycin may work by eliminating neutrophils.

“There are topical agents coming out soon that I believe will treat rosacea very effectively,” he says.

The labels for all existing topical agents used in rosacea say that these treatments will relieve erythema. “But that’s always perilesional erythema,” Dr. Webster says. Pimples can cause erythema around them, “And if you make the pimple go away, that erythema goes away. But that’s a far cry from saying you can make the blushing red cheeks of a patient with rosacea return to normal by using topical metronidazole if there are no pimples.”

However, he says the topical vasoconstrictor oxymetazoline is very effective in relieving erythema (Shanler SD, Ondo AL. Arch Dermatol. 2007;143(11):1369-1371), as is brimonidine, which is used for glaucoma.

Regarding rosacea, “I’ve had patients who have had flushing so severe that they couldn’t go outdoors in winter because they would be in agony from the burning of their cheeks due to flushing. These drugs relieved that completely. I’m optimistic that we’ll have them approved for rosacea in the next couple years,” he says.

As for tretinoin, he says that according to one study, long-term use of this drug appears effective against rosacea (Ertl GA, Levine N, Kligman AM. Arch Dermatol. 1994;130(3):319-324).

“The problem with that paper is that it’s very hard to separate the symptoms of chronic sun damage from those of erythrotelangiectatic rosacea. It’s clear that topical tretinoin improves sun damage, and it may improve rosacea. But I tend to avoid it because of its irritating quality,” to which patients with rosacea might be especially susceptible, Dr. Webster says.

Steroid action

Although steroid-induced rosacea isn’t new, many more patients are using topical steroids, whether they know it or not, Dr. Webster says. “Many homeopathic creams have been shown to have vasoconstrictor activity. There’s often clobetasol in there, either honestly or surreptitiously.”

Dr. Webster says if a dermatologist suspects steroid-induced rosacea in a patient with no apparent steroid exposure, “Quiz the patient about all the facial products he or she is using. A tipoff is rosacea under the nares. When you see pimples under the nose, think of steroid use first.”

In treating steroid-induced rosacea, “I used to be gentle,” gradually stepping patients down to increasingly weaker steroids, Dr. Webster says. “But I never got anybody better that way. Now, I stop the steroids cold and tell patients they’re going to have a bad month.” Dr. Webster also puts patients on topical tacrolimus and an oral antibiotic such as doxycycline, “And this regimen generally works.”

Finally, Dr. Webster says, it’s well established that patients with rosacea have a defective skin barrier that renders them especially susceptible to burning and stinging in response to topical products. Methods including measurements of transepidermal water loss (TEWL) have successfully documented the presence of barrier malfunctions in rosacea. “Moisturizing alone can improve the TEWL,” as well a patient’s burning and stinging symptoms, he says.

Skin conditions marked by excessive permeability activate serine proteases, Dr. Webster says. “And serine proteases such as kallikrein have been shown to cleave cathelicidin (Yamasaki K, Di Nardo A, Bardan A, et al. Nat Med. 2007;13(8):975-980. Epub 2007 Aug 5), which is an antimicrobial peptide in the skin.” Additionally, research has shown that in patients with rosacea, cathelicidin is cleaved in an unusual way and deposited in the skin, thereby causing inflammation (Schauber J, Gallo RL. J Allergy Clin Immunol. 2009;124(3 Suppl 2):R13-R18).

“If we can stop the cleaving and deposition of this peptide, that in theory should make rosacea better,” Dr. Webster says. This possibility raises the question of whether treating rosacea reduces skin irritability. In a phase 2 study, using metronidazole gel for two weeks greatly improved symptoms such as burning, stinging, redness and roughness in patients with rosacea.

“Probably, the barrier dysfunction and the rosacea go hand-in-hand. If you fix one, you fix the other,” he says.

Furthermore, he says, facial inflammatory diseases such as atopic dermatitis, seborrheic dermatitis and rosacea can overlap.  In such cases, he says patients must follow the usual treatment recommendations such as avoiding irritants for rosacea and seborrheic dermatitis. “But I find that off-label use of ciclopirox, tacrolimus or pimecrolimus works particularly well for the non-rosacea inflammatory disease,” making their rosacea more treatable.

Oral treatments

Dr. Webster says physicians have long prescribed tetracyclines, which have direct anti-inflammatory effects.

“We also use other antibiotics that presumably also work through an anti-inflammatory mechanism,” he says. “There’s no organism that we know for sure is active in causing rosacea. The thought that maybe Demodex is involved is still a possibility,” although evidence here is weak. Nevertheless, he says the antibiotics that work well for rosacea do not kill this organism.

Regarding other antibiotics, “Ciprofloxacin works occasionally,” but Dr. Webster says dermatologists should reserve this medication - as well as Bactrim (sulfamethoxazole, trimethoprim; AR Scientific) - for patients who fail less potent therapies. “Both of these are useful for serious infections, and we don’t want to be prescribing them indiscriminately,” he says.

Among beta blockers, propranolol sometimes works for rosacea flushing (Craige H, Cohen JB. J Am Acad Dermatol. 2005;53(5):881-884). “But other beta blockers have tended to fail. Interestingly, antidepressants, namely SSRIs, will occasionally work in a patient who presents with rosacea and depression. It always amazes me, but maybe once a year I see someone who gets better on a drug like Paxil (paroxetine, GlaxoSmithKline),” Dr. Webster says.

Prescribing Accutane (isotretinoin, formerly manufactured by Roche) for rosacea is off-label.  “The iPLEDGE pregnancy prevention program doesn’t forbid you from using it off-label. But if you do, you must tell the patient you’re using it in a rather novel way, and document this discussion in your chart,” Dr. Webster says. Otherwise, dermatologists might fall victim to lawsuits.

“Accutane is useful for nodular, inflammatory rosacea. However, it doesn’t seem to do much with mild rosacea. And how it works is a mystery,” although isotretinoin does have anti-inflammatory properties, he says.

In acne, isotretinoin reduces sebum. “But as far as we know, sebum doesn’t play any certain role in rosacea,” Dr. Webster says. Nevertheless, isotretinoin works for rosacea. “It’s sometimes useful in rhinophyma, but not when the nose has gotten fibrotic.” He says low doses (about 10 mg daily) generally suffice.

Unlike in acne, he says, “Isotretinoin is not curative in rosacea. In acne, 80 percent of patients who go on an adequate dose of isotretinoin never have acne again. But when you take a patient with rosacea off isotretinoin, the disease will return if you don’t have the patient on something else to suppress it.” DT

Disclosures: Dr. Webster has been a speaker, investigator and/or consultant for Galderma, Allergan, Cutanea Life Sciences, Medicis and Valeant.