Thought leaders in the realm of acne and rosacea therapies weigh in on their approaches to care and offer their perspective on the future direction of care for these conditions. Ahead, Julie Harper, MD, Todd E. Schlesinger, MD, Linda Stein Gold, MD, and James Ulery, MD share their insights.
As understanding of the pathophysiology of acne has evolved in recent years, has your approach to treating acne changed?
Todd E. Schlesinger, MD, Director, Dermatology & Laser Center of Charleston Center for Clinical Research, SC says two factors have affected his treatment of acne. One is the recognition of inflammation and the nature of how it is seen before the development of the active acne lesion. The other is the importance of barrier dysfunction in skin disease, explaining that barrier dysfunction may be related to the disease state acne itself, or due to treatment. Dr. Schlesinger says he has increased his use of combination topical agents and hormonal modifying agents and tried to reduce the use of oral antibiotics. “I have also focused on topical agents with lower irritancy profiles, combining the best of the various mechanisms of action into a unified treatment regimen,” he adds.
Inflammation throughout the life cycle is now considered an important target, explains Julie Harper, MD, Clinical Associate Professor of Dermatology at the University of Alabama-Birmingham. “Consider that we still refer to comedonal acne lesions as ‘non-inflammatory lesions’ and you can see just how new this concept really is. Comedonal lesions are inflammatory lesions and we need to address inflammation any time that we are addressing acne,” Dr. Harper says, adding that it’s interesting that many medications used to treat comedonal acne lesions also have anti-inflammatory properties.
James Ulery, MD, President of Skincare Associates PC in Monroe, MI, concurs about the significance of the role of inflammation in all stages of acne, saying that even micro-comedones significant inflammatory infiltrates have been noted.
“Now I look at medications for both their traditional benefits and any anti-inflammatory benefits,” says Dr. Ulery. “So Differin, for instance, many years ago had data that the molecule had significant anti-inflammatory properties that Retin A did not have. For patients beginning the acne adventure or with significant erythema, I prefer to start with Differin. For many patients, I consider adding low-dose doxy early, or now more regularly have to choose between benzoyl peroxide (BPO) washes versus sulfacetamide washes, which have very different therapeutic ends. I am also glad that there is more data about diet and acne, so we may have better discussions about therapy and less about mythology.”
Dr. Schlesinger says that he mostly has patients use products containing a benzoyl peroxide and a topical antibiotic in combination with anti-inflammatory agents, such as topical dapsone. “I have also shifted somewhat to the use of retinaldehyde as a less irritating alternative to the traditional tretinoin in its various forms. However, there are some very powerful tretinoin formulations with low irritancy that I also use. For adult females with perceived hormonally induced acne, I have frequently employed spironolactone with proper monitoring with good success. For body acne, the combination treatments also work well along with a mild exfoliant. I also provide the patient with an application aid to assist them in reaching areas of the body outside their usual range of motion,” he says. “The use of suction based facial treatments in combination with blue and red light emitting diode therapy has also entered my armamentarium for the treatment of acne. Getting the process started by removing oils, infusing anti-inflammatory proteins and using light therapy to reduce bacterial presence seems to help in my experience.”
Linda F. Stein Gold, MD, Director of Dermatology Clinical Research at the Henry Ford Hospital in Detroit, says, “My goal is to get my acne patients under control as quickly as possible. Generally for moderate to severe patients I will use a potent topical agent in combination with an oral antibiotic.” However, she says her approach to long-term maintenance has changed in recent years and her goal is to stop oral antibiotic use as quickly as possible—generally in four to six months.
How and why do you choose specific treatments for acne patients? Does prevention of scarring play a role?
Dr. Schlesinger says he chooses specific treatments that cross the mechanism of action spectrum in combination to provide the best long term and sustainable control. “Acne scarring is caused by the collagen remodeling process, after it is broken down by collagenase associated with inflammation. Any way I can control the inflammatory component of acne earlier, helps to prevent scarring before it begins,” Dr. Schlesinger says. “For this reason, if a patient presents with acne that I feel has the potential to result in scarring, I do not hesitate to offer isotretinoin as an option to the patient. “
“The selection of a treatment plan is based on many factors. I consider the type and severity of acne, response to prior treatments, patient preference and patient motivation,” says Dr. Harper. “Any time that there is evidence of scarring, my treatment approach becomes aggressive. Scarring is easier to prevent than to treat.”
Dr. Ulery explains that his acne treatment choices are based on three factors: the type of acne activity the patient has, what the patient has used previously/currently, and what the insurance company will let the patient have.
For patients who are concerned about scarring or who have evident scarring, Dr. Ulery also treats aggressively, but explains to patients that scars may be permanent a but some medications and time may allow remodeling, which will improve appearance. For patients with milder acne, he reminds them that their acne will not scar but squeezing lesions could result in scarring.
Dr. Ulery says that he tries to start all of all of his acne patients with retinoids as a foundation. “Differin or Epiduo are far less initially irritating that Retin A and they have anti-inflammatory effects, so for many patients that is our entry point. In 6-12 weeks we very well may increase to higher strength retinoids or we may treat regionally, i.e., Epiduo on the face and RetinA/Tazorac on the back and shoulder,” he says. “For the most part, I prefer to consider treatments that fall into normal activity patterns: BPO wash (rather than leave on) with the morning and evening shower, retinoid at night, and topical antibiotics, which can be portable and used before and after sports.”
He adds that when a patient has significant inflammatory papules or pustules on presentation, he always starts the retinoid and an oral antibiotic concurrently, using first line drugs and making adjustments if sun sensitivity is an issue. When considering Isotretinoin, he says a month trial of Bactrim can have amazing results. For patients who present with cysts or fairly massive acne activity, he discusses Isotretinoin and begins that process, but will also prescribe an oral antibiotic to cool them down a bit.
What role does concern about antibiotic resistance play in your decisions?
“I am always cognizant of the importance and possibility of antibiotic resistance particularly when we are seeing more broadly resistant bacteria in hospitals and internationally,” offers Dr. Ulery. “This issue has been brought about since early 2000 and is again being discussed from dermatology groups and the CDC. I limit antibiotic usage to the shortest reasonable duration. In the case of rosacea and acne, usually only one-month scripts and then evaluate for effect. I do not use long-term oral antibiotics, even those stated be subantimicrobial. I consider antibiotics for their therapeutic spectrum and anti-inflammatory effect, and use them while I am waiting for other treatments to kick in.”
Dr. Stein Gold, who aims to take patients off of oral antibiotic therapy after four to six months says, “We have good studies that have shown that in a significant number of patients we can stop the oral antibiotic and continue on topical therapy alone with continued control of their acne.”
Dr. Schlesinger says the issue of antibiotic resistance is a bigger concern for his patients than himself. “However, I do think that it is a valid concern and try to limit the use of oral antibiotics when possible. I also focus on using the medications specifically tailored for acne and appreciate the availability of weight-based dosing.”
Dr. Ulery points out that research that has been recently brought out in meetings is that fact that resistance to minocycline (and probably tetracycline class antibiotics in general) is far less likely due to the nature of the chemical than other classes of antibiotics.
Does treating rosacea call for a multifactorial approach? What is the role of Demodex in rosacea?
“Treating rosacea is definitely multifaceted. It is vital to educate patients about rosacea and to discuss potential trigger factors. Prescription medications and procedural treatments are not meant to override the necessity of trigger avoidance,” says Dr. Harper. “Successful management of rosacea involves appropriate skin care, elimination or mitigation of triggers, prescription medications, and sometimes procedural or device-based treatments. Demodex is likely a trigger factor in many rosacea patients. Demodex or a component of Demodex may upregulate innate immunity, promoting inflammation in rosacea subjects.”
“Rosacea has a spectrum of presentations. On the one hand, you have erythema and on the other hand you have papules and pustules. Treatment should address both presentations when demonstrated in the same patient,” explains Dr. Schlesinger “One consideration is the effect of barrier dysfunction. It has been shown through published studies that rosacea responds to compounds such as low molecular weight hyaluronic acid (LMWHA) that not only improve barrier function, but increase the level of beta 2 defensins, that impair demodex mites and reduce inflammation. Clinical relevance is demonstrated by the reduction in erythema scores and subject satisfaction assessments.
Demodex has the role of stimulating the already abnormal innate immune system present in rosacea patients. Elevated levels of cathelecidins are pushed higher by the antigens present in Demodex mites via a toll-like receptor mediated pathway.”
Dr. Ulery says that treating erythema of rosacea is always challenging, and he typically discusses layering medications for their effect. “The first line drugs of metronidazole topically with or without sulfer based washes have both anti-inflammatory and antibacterial effects that work for many people, but take time to see maximum effect (I tell patients about three months),” he says. He adds that brimondine (Mirvaso) can effectively help to hide erythema for about 10 hours, but that it does not essentially treat or change anything. An underlying treatment is still needed.
“Oracea (doxycycline), which has documented anti-inflammatory effects is also useful for redness and mild to moderate inflammatory lesions with less potential side effects. Some patient still will do better with short-term (one month or less) dosing of Minocin or Doxy at 100mg twice daily,” he adds.
For telangiectasia, Dr. Ulery recommends Mirvaso, coverup makeup, diode laser, or intense pulsed light therapy. He says ivermectin (Soolantra) is an interesting and novel approach to Rosacea and that it purportedly has direct anti-inflammatory effects.
“I think Demodex is a bit overplayed as a causative agent in rosacea and more likely will bring in patients with delusions of parasitosis,” Dr. Ulery says. “There have been studies in the past that did show some associations with the presence of H. Pylori correlating with rosacea, and treatment for H. Pylori resulting in improvement in rosacea (although oral metronidazole was used in those cases). The idea of localized infection triggering inflammation either systemically or locally does have some interest and plausibility.”
Has your approach to treating rosacea shifted as new medications have become available?
“With the approval of 1% ivermectin cream and its efficacy and safety in the treatment of patients with moderate to severe PPR, the role of Demodex has been more closely questioned,” explains Dr. Stein Gold. “Ivermectin has both anti-inflammatory and anti-parasitic properties and it is unknown what the mechanism of action is in rosacea. I feel that both mechanisms will likely play a role as we have had great anti-inflammatory agents in the past for rosacea yet ivermectin has superior efficacy and the potential for long-term remission. It is important to have drugs that treat both the inflammatory lesions as well as the background erythema in order to get our patients truly clear.”
Dr. Harper says she is thankful to have an FDA-approved product that targets the persistent facial erythema that many rosacea sufferers struggle with. “My overall approach to treating rosacea has not changed but my armamentarium has enlarged!”
Dr. Schlesinger says he also has begun to use some of the new therapies available when indicated. “Treatments specifically directed at erythema are combined with those aimed at the papulopustular component of the disease,” Dr. Schlesinger explains. “These, combined with barrier repair medications and sunscreen are important components of a complete treatment regimen. I also combine plant-based cosmeceuticals to reduce redness and retinaldehyde to control epidermal function, inflammation and redness.”
Dr. Ulery says he uses ivermectin (Soolantra) for patients who are not getting good results with Finacea or Metrogel, who want to see what is new on the market, or who are reticent about oral antibiotics. He says he uses Mirvaso for patients who find erythema at work or social occasions problematic, as needed. He adds that he may prescribe Oracea for one to two months to cool down an active rosacea flare or when a patient has a special occasion in a month and want to avoid a flare. He prescribes this with concurrent topicals and stops oral medications as quickly as is reasonable.
“I still do a lot of discussion about triggers identification and avoidance, flare treatment versus maintenance treatment, and to keep the regimen of cosmetics and other agents as simple as possible,” Dr. Ulery adds. “Higher dose oral antibiotics are for significant flares and again a month or two before moving off.”
Where do device treatments fit into the overall care of acne and rosacea?
“I think devices are great adjunctive treatments for some patients. Specifically diode laser/vascular laser for fixed telangiectasia, IPL broadly for erythema, blue/red light for inflammatory lesions. The biggest issue with devices are that most insurance plans do not cover their use for these indications, so it becomes an out of pocket cost for patients,” says Dr. Ulery, adding that the at-home device market has grown rapidly. “It will be hard to justify the devices as part of standard of care, but with more commercial availability, the use of devices will probably increase over time. I do think some old therapies, which are now being covered by insurance for acne, such as “acne surgery” and glycolic chemical peels for acne may become more common again. Ultimately we may have great combinations of topical meds with IPL that will dramatically shorten times to improvement, it just has to be accessible and affordable.”
Dr. Harper concurs that insurance coverage is a hurdle and says she doesn’t currently use devices to treat acne. “As the cost of prescription medications increases and shifts to the patient, these procedural treatments may become more cost-effective. I am always interested in cost-effective treatments that are safe, well-tolerated, and that yield long-term control of disease,” she adds. “I do use a pulsed-dye laser for erythema and telangiectasia associated with rosacea.”
Dr. Schlesinger says “Lasers such as the pulsed dye, have excellent utility in treating the erythema associated with rosacea. For acne, I use a combination of vacuum suction and microdermabrasion with infusion. There are many novel devices being evaluated. I see these playing a larger role in our repertoire of acne treatments.”
In terms of prescribing treatments for acne and rosacea, how much do insurance plans and co-pays affect your choices?
“Unfortunately, insurance coverage plays a large role in treatment choices,” says Dr. Harper.
“We have seen a sharp rise in generic costs,” adds Dr. Schlesinger. “Often, a brand name medication with a strong co-pay assistance program may benefit the patient.”
“Dealing with insurance plans and pharmacies are the single biggest problem for my patients, my staff, and my self. It is unimaginable how many hours a month are spent are trying to figure out which medication the insurance plan will let the patient have, which pharmacy will provide the best price for the patient, and whether the pharmacy or insurance will substitute the prescription that we will not know about,” offers Dr. Ulery. “Certainly higher copays or deductibles for pharmacy benefits are driving patient choice in many cases. The only good news is that since many generic drugs have good to stratospheric levels in the last two years, the price of branded drugs (with copay cards) is now often far more affordable for the patient, and provide the benefit of predictable dosing and delivery mechanism. In some cases the mail order pharmacies have become a great partner for patients and my practice by facilitating drug access, minimizing patient cost, and minimizing phone calls/paper work for my staff. It may be that dermatology specific pharmacies will be one solution for the plethora of issues we find with local and retail pharmacies. Insurance copay and deductible issues have also affected patient behavior: Patients tend to not want to come to follow up visits, patients tend to wait until the condition is much more active or flared before coming in, and it is not uncommon for patients who were last seen a few years ago to call demanding prescriptions but they do not want to come in to be examined.”
What barriers still stand in the way of effective care and how can industry and educational curricula begin to address these?
“Furthering our understanding of the etiology of rosacea will drive the development of new therapies. The biggest barrier is understanding that rosacea is multifactorial and addressing all the components will produce better results,” says Dr. Schlesinger.
Dr. Harper adds, “There are many individuals with acne and rosacea who never seek treatment. Some of these individuals may have mild disease that they are managing on their own. Many simply go undiagnosed and untreated. It is important to educate the population about these conditions and to dispel myths that are so prevalent. We also need to educate primary care providers to recognize and treat these conditions. Access to prescription medicines is also vital. Acne and rosacea are not cosmetic conditions and they should not be treated as such.”
Dr. Ulery says it would be valuable to introduce an educational curricula to older elementary and middle school children to educated them about acne. “Too many students believe TV commericals or common myths about acne and fail to use their time or money in truly effective ways. If we reach out and educate them when the process is beginning, we may make a better impact,” Dr. Ulery explains. “Certainly industry also needs to lead the way in some of this outreach by targeting the ads and education at this younger group rather than the late teens that I usually see.”
On the rosacea side, Dr. Ulery says industry needs more disease state discussion and information for patients, along with advertisements that feature people who really look like patients who would have rosacea.
“It would be great if apps were designed to remind patients when to use their medications as well as remind them that if the condition is not better at a specified interval that they should follow up with their dermatologist,” says Dr. Ulery.
Is our understanding of the pathophysiology of disease translating to better treatments?
“Absolutely! The more clearly we define the pathophysiology of acne and rosacea the more targeted our treatments will be,” says Dr. Harper.
Dr. Schlesinger says research has supported new understanding of the pathophysiology of rosacea. “This level of knowledge has broadened our scope of thought with respect to rosacea and certainly brought new treatments. In the past few years, basic science and clinical researchers have focused on abnormalities seen in the innate immune system in rosacea. The innate or conserved immune system is the pathway that is not learned, and includes the toll-like receptor (TLR) pathways. There have been new medications, such as LMWHA topicals as well as those aimed at Demodex mites. By targeting the innate immune dysfunction either directly (LMWHA) or indirectly (ivermectin), we have seen clinical improvement in rosacea patients.”
Dr. Ulery adds, “I am excited about the prospect of topical minocycline – because it will likely have the advantages of strong anti-inflammatory effect along with an antibiotic effect, which will be far less susceptible to resistance than current topical antibotics. Certainly many of us are looking at the mechanisms of effect of the drugs and how to combine or pair them for synergy. There is renewed excitement and interest in new topicals, oral meds, devices, and cosmetic treatments. Hopefully we will further refine our understanding to permit more targeted therapy such as we are seeing with biologics and psoriasis.”