W hen the Journal of the American Academy of Dermatology published consensus recommendations on the treatment of acne just over a year ago, a number of experts hailed them as an approach that was long overdue. The recommendations, which were issued by the Global Alliance to Improve Outcomes in Acne and were published in a supplement to the JAAD that was sponsored by an educational grant from Galderma, called for a change in the way that many dermatologists treat inflammatory acne. What Did Top Acne Treatment Experts from Around the World Recommend? When discussing what they thought should be standard acne treatment protocols, the experts stressed the following key elements: 1. Dermatologists should use topical retinoids as a first-line therapy for all forms of mild to moderate acne, not just comedonal or non-inflammatory acne. 2. Combination therapy that includes a topical retinoid plus an antimicrobial is the most effective initial approach. Once control is achieved, they say, many patients can be maintained on topical retinoids as sole therapy. 3. While systemic antibiotics remain an important class of therapy, the recommendations call for dermatologists to use these drugs for as short a period of time as possible because of concerns about emerging resistance. The recommendations are supported by a substantial body of evidence from clinical trials. But dermatologists who participated in the conference that produced the recommendations also say that the recommendations raised questions about how many dermatologists around the world will change their longstanding behaviors when it comes to treating acne. Paradigm Shift For many dermatologists, using retinoids to treat inflammatory acne may seem counterintuitive. These drugs, after all, can potentially cause significant irritation in the initial course of treatment, so why use them on a patient who is already inflamed? The simple answer is that study after study has proven that topical retinoids, even as monotherapy, can clear patients with inflammatory acne or all types of acne effectively and keep the condition at bay more effectively than antibiotics alone. The recommendations point to the science — much of it 30 years old — showing that topical retinoids not only efficiently eliminate blackheads and whiteheads, but that they attack acne at the microcomedo level. As a result, they call on dermatologists to use topical retinoids as a first-line therapy to treat all forms of acne, not just comedonal forms of the disease. “We think that topical retinoids can be used alone for comedonal activity,” explained Alan R. Shalita, M.D., Professor and Chairman of Dermatology at the State University of New York and Downstate Medical Center in Brooklyn. “For inflammatory acne, many papers show that topical retinoids used with an antibacterial agent are more effective than the antibacterial agent alone.” John E. Wolf Jr., M.D., Professor and Chairman of the Department of Dermatology at Baylor College of Medicine, said that for many dermatologists, the recommendations will represent a “paradigm shift.” While the recommendations do not tell dermatologists to stop using antimicrobial therapies for acne, they do call on physicians to use antimicrobial therapies as second-tier therapies, and in conjunction with retinoids. Experts on the panel that produced the recommendations realize that they are contradicting the practice habits of many dermatologists. “We’re very comfortable with the idea of using antibiotics because they’re safe and effective,” explained Neil Shear, M.D., the Helen and Paul Phelan Professor of Dermatology and Chief of Dermatology at the University of Toronto Medical School. “But the whole idea of drug resistance because of antibiotic use is a real one with serious public health implications.” “One of the arguments for discontinuing antimicrobial therapies as soon as possible is that they may lead to antibiotic resistance,” explained Dr. Wolf. “One concern is that you may encourage resistance of Propionibacterium acnes. Another concern is that you may develop resistance to other bacteria like Staphylococcus aureus that are medically more significant than P. acnes alone.” “The consensus was that if you needed to use an antimicrobial on a long-term basis,” Dr. Wolf continued, "you should use a benzoyl peroxide product or that product in conjunction with antibiotics. In both cases, you’ve got less of a resistance issue. “With benzoyl peroxide,” he said, “there’s no evidence of antibiotic resistance. And with the combination of benzoyl peroxide and antibiotics, there’s less resistance than with antibiotics alone, and there’s no evidence of resistance induced by a topical retinoid.” While the recommendations call for less use of antimicrobials, the drugs are still an important part of therapy for treating acne. Retinoids attack acne at its root by targeting the comedones, but antimicrobial therapy can help reduce inflammation, speeding up the clearing process. “If you use the antimicrobials, either a benzoyl peroxide or an antibiotic, they are going to add additional anti-inflammatory activity, and they’re going to kill the P. acnes’ organisms,” Dr. Wolf said. “You’re attacking as many as possible of the different mechanisms that lead to the development of acne. The topical retinoids are literally attacking the root because the microcomedo is the earliest step of the evolution of acne.” Dr. Wolf added that numerous studies have shown that combination therapy pairing topical retinoids with antimicrobials is more effective than antimicrobial therapy alone. One large study, he pointed out, showed that when adapalene was combined with agents such as topical clindamycin or oral doxycycline, there was a significant increase in anti-acne activity. Old News? In many ways, the “news” about the ability of topical retinoids to treat inflammatory acne is not news at all. Dr. Shalita, for example, pointed out that studies published in the early 1970s convincingly showed that topical retinoid therapy was effective in treating inflammatory acne. James J. Leyden, M.D., Emeritus Professor of Dermatology at the University of Pennsylvania School of Medicine, had a hand in many of those early studies. While the role of retinoids in treating acne may be old hat to him, he said that for many dermatologists, the idea of using the agents for inflammatory acne is still new. If studies have shown that topical retinoids so effectively treat acne for three-plus decades, why haven’t dermatologists embraced the therapy sooner? In large part, experts say, many physicians never got past the idea that topical retinoids can cause irritation. “The consensus was that some of the retinoids like tazarotene can be quite inflammatory,” explained Dr. Shear. “When you have something that is quite inflammatory, you don’t tend to think of it as potentially anti-inflammatory.” He admitted that he was surprised by some of the data on the efficacy of retinoids in acne the panel reviewed in drafting the recommendations. “You immediately think of antibiotics to try to calm down inflammation,” Dr. Shear said, “but the retinoid idea is a good one. I’ve found that it has changed the way I practice.” Dr. Leyden said that another trend — the emergence of topical antibiotics to treat acne — in large part eclipsed the role of retinoids. Topical antibiotics were so heavily promoted as go-to drugs to treat inflammatory acne that many physicians simply never gave retinoids a chance in patients with inflammatory acne. “We had the topical antibiotic people saying that if you have inflammatory acne, use this class of drug and don’t use retinoids,” Dr. Leyden explained. “The idea that you should use both drugs in all types of patients, which I had helped demonstrate in 1973, got lost in the shuffle. It’s one of the major reasons that something that is now considered a new concept is actually an old concept. Perhaps its time has finally come.” Dr. Shalita said he thinks of the new recommendations as not presenting new information, but instead “re-emphasizing” what many probably know but have not put into practice. He also noted that one common misconception that may be keeping some dermatologists from using topical retinoids is that some think that benzoyl peroxide is a comedolytic. While it’s true that antibacterials reduce comedones, he said, they don’t have a direct comedolytic action. Instead, they have an effect on cytokines, which can induce comedones. The net clinical effect is a modest reduction in non-inflammatory lesions. Irritation and Long-Term Maintenance Despite a solid body of evidence reaching back more than three decades and recommendations from a star-studded panel, there are questions about when — and if — dermatologists will embrace the therapy. Some, like Diane Berson, M.D., Assistant Professor of Dermatology at Cornell Medical College, are optimistic that more dermatologists will start using topical retinoids to treat all forms of acne. “I think that more dermatologists are beginning to accept and understand the notion that topical retinoids have anti-inflammatory properties,” she said, “and that you therefore do not have to wait until the inflammatory component is under control to add them to the regimen. You can start these drugs right away.” While the original generation of retinoids may have received a bad rap as irritating, there have been significant changes in the drugs that make many easy to use. “The newer generation of topical retinoids and newer formulations of older formulations are less irritating than the first generation,” Dr. Wolf explained. “This is very significant because irritation with the use of topical retinoids has been a problem in terms of patient compliance, because they would often cause redness and dryness and peeling and itching and burning and stinging of the skin.” Dr. Leyden took that view a step further, saying that while some patients will experience irritation, it’s not enough of an issue to keep dermatologists from prescribing topical retinoids. “There’s no question that there are some patients who have trouble with topical retinoids, even the modern-day cream formulations,” he said. “They’re a small percentage, but clearly they exist.” Most patients who experience any reaction, however, will experience much more minor — and temporary — effects. “There is a significant group of people who struggle for the first week or two,” Dr. Leyden said. “But if you understand that the drugs work, you can get patients to use them correctly, and they really are complementary to antibiotics.” Irritation from topical retinoids, he added, should not keep dermatologists from using the drugs. “The irritation that most people experience is not worth talking about,” Dr. Leyden explained. “You need to tell patients up front that they may have some trouble during the first week or so of treatment. You explain that if they have trouble during the first week or so to stop and use the drug every other day, to tiptoe into the water.” To be truly effective in treating acne, however, retinoids need to be used on an ongoing basis as part of a maintenance therapy. While maintenance therapy is an entrenched part of dermatology for conditions like eczema and psoriasis, experts say that many physicians take a somewhat different view of treating acne. “Many dermatologists over the years have had a tendency to treat acne until it clears up and resolves,” Dr. Wolf said, “and then essentially discontinue treatment until the patient has a flare-up. Now we are recommending strongly that once a patient has been brought under control by the combination therapy, the antimicrobial agents should be discontinued and the topical retinoids should be maintained for what can be a fairly significant period of time to prevent recurrences of the acne.” The rationale for prescribing a maintenance therapy of retinoids gets back to the mechanism through which retinoids clear up acne. “The theory behind that last recommendation is that topical retinoids act on the microcomedo as well as through their anti-inflammatory properties,” Dr. Wolf said. “They are clearly the most effective of our agents for eliminating microcomedones, and the microcomedo is the earliest step in the evolution of acne.” Dr. Wolf pointed to a German study that found while tretinoin helped reduce microcomedones significantly, microcomedones began to flare up again once the retinoids were discontinued. “The study suggests that if you don’t maintain the use of a topical retinoid, the microcomedones will form again and lead to other acne lesions.” The only problem with maintenance therapy is that it is often difficult to convince patients to continue treatment once their acne is cleared. If the physician takes the time to explain the benefit to patients, however, patients will achieve greater compliance with a maintenance program. Rethinking a Disease As a result, the recommendations call on physicians — and their patients — to essentially rethink the way they treat acne. “Dermatologists have to believe that this is beneficial,” Dr. Wolf said, “because they and their staff will have to take the time to tell patients why they want them to keep using one of these products even though their acne looks good.” Dr. Leyden acknowledged that using topical retinoids to treat inflammatory acne takes time, particularly during the initial visit. “You have to make sure that people understand,” he explained. “You can’t just write a couple of prescriptions and say goodbye. After that it’s pretty easy, but it does take some time up front, and time has become precious.” “For patients’ sake,” Dr. Berson said, “it’s better to have them using a therapy that will keep them clear instead of making them deal with treatment again. For both physicians and patients, maintenance is easier than having to treat again. “It’s analogous to eczema patients,” she continued. “We treat them with steroids, but when they’re clear, we explain to them that they need to keep their skin lubricated with a moisturizer to prevent the eczema from coming back instead of treating it every time it flares.” Still, Dr. Berson acknowledged that the pressures of modern practice may leave some dermatologists less than enthusiastic about taking time out of their busy schedule to educate patients — even if it does ultimately free up more of their time in the long run. “With managed care and the general craziness of practice, many physicians may find that it’s harder to spend more and more time with patients,” she said. “When you have to explain a treatment regimen to patients, it is more work.” And Dr. Shear said there will undoubtedly be caution on the part of dermatologists as they try what to them is a new approach. Some will prescribe retinoids to four or five patients and then carefully watch for results. “If nobody gets better,” he said, “some will say, ‘I don’t believe this works.’ It’s the same thing if you use a treatment and get irritation in the first three or four patients. It’s a lot harder to prescribe it to the fifth patient.” Dr. Wolf said that patients may also resist retinoids, in part because of cost: “People may tell you, ‘I spent $120 on this gel or cream and my face got red,’” he explained. “Maybe they were overzealous and didn’t follow the directions properly, but if you see that sort of inflammation, you’re going to be a little cautious.” Even Dr. Leyden acknowledged that unless dermatologists have seen the effects of topical retinoids on these patients first-hand, they may have difficulty believing that a simple shift in strategy can produce such dramatic results. But he also pointed to a challenge that is bigger than convincing dermatologists to use a “new” class of drugs to treat acne, and that is changing their mindset about the disease itself. “I think a lot of dermatologists don’t like to treat acne,” he said, “and that’s a shame, because it can be a tremendous source of satisfaction. You see kids who are social recluses and almost depressed really bloom when they receive treatment. And after you’ve been practicing long enough, some of those people bring their teenagers to you and tell you how important it was for them to get treated and get better.”
Should You Change the Way You Treat Acne?
W hen the Journal of the American Academy of Dermatology published consensus recommendations on the treatment of acne just over a year ago, a number of experts hailed them as an approach that was long overdue. The recommendations, which were issued by the Global Alliance to Improve Outcomes in Acne and were published in a supplement to the JAAD that was sponsored by an educational grant from Galderma, called for a change in the way that many dermatologists treat inflammatory acne. What Did Top Acne Treatment Experts from Around the World Recommend? When discussing what they thought should be standard acne treatment protocols, the experts stressed the following key elements: 1. Dermatologists should use topical retinoids as a first-line therapy for all forms of mild to moderate acne, not just comedonal or non-inflammatory acne. 2. Combination therapy that includes a topical retinoid plus an antimicrobial is the most effective initial approach. Once control is achieved, they say, many patients can be maintained on topical retinoids as sole therapy. 3. While systemic antibiotics remain an important class of therapy, the recommendations call for dermatologists to use these drugs for as short a period of time as possible because of concerns about emerging resistance. The recommendations are supported by a substantial body of evidence from clinical trials. But dermatologists who participated in the conference that produced the recommendations also say that the recommendations raised questions about how many dermatologists around the world will change their longstanding behaviors when it comes to treating acne. Paradigm Shift For many dermatologists, using retinoids to treat inflammatory acne may seem counterintuitive. These drugs, after all, can potentially cause significant irritation in the initial course of treatment, so why use them on a patient who is already inflamed? The simple answer is that study after study has proven that topical retinoids, even as monotherapy, can clear patients with inflammatory acne or all types of acne effectively and keep the condition at bay more effectively than antibiotics alone. The recommendations point to the science — much of it 30 years old — showing that topical retinoids not only efficiently eliminate blackheads and whiteheads, but that they attack acne at the microcomedo level. As a result, they call on dermatologists to use topical retinoids as a first-line therapy to treat all forms of acne, not just comedonal forms of the disease. “We think that topical retinoids can be used alone for comedonal activity,” explained Alan R. Shalita, M.D., Professor and Chairman of Dermatology at the State University of New York and Downstate Medical Center in Brooklyn. “For inflammatory acne, many papers show that topical retinoids used with an antibacterial agent are more effective than the antibacterial agent alone.” John E. Wolf Jr., M.D., Professor and Chairman of the Department of Dermatology at Baylor College of Medicine, said that for many dermatologists, the recommendations will represent a “paradigm shift.” While the recommendations do not tell dermatologists to stop using antimicrobial therapies for acne, they do call on physicians to use antimicrobial therapies as second-tier therapies, and in conjunction with retinoids. Experts on the panel that produced the recommendations realize that they are contradicting the practice habits of many dermatologists. “We’re very comfortable with the idea of using antibiotics because they’re safe and effective,” explained Neil Shear, M.D., the Helen and Paul Phelan Professor of Dermatology and Chief of Dermatology at the University of Toronto Medical School. “But the whole idea of drug resistance because of antibiotic use is a real one with serious public health implications.” “One of the arguments for discontinuing antimicrobial therapies as soon as possible is that they may lead to antibiotic resistance,” explained Dr. Wolf. “One concern is that you may encourage resistance of Propionibacterium acnes. Another concern is that you may develop resistance to other bacteria like Staphylococcus aureus that are medically more significant than P. acnes alone.” “The consensus was that if you needed to use an antimicrobial on a long-term basis,” Dr. Wolf continued, "you should use a benzoyl peroxide product or that product in conjunction with antibiotics. In both cases, you’ve got less of a resistance issue. “With benzoyl peroxide,” he said, “there’s no evidence of antibiotic resistance. And with the combination of benzoyl peroxide and antibiotics, there’s less resistance than with antibiotics alone, and there’s no evidence of resistance induced by a topical retinoid.” While the recommendations call for less use of antimicrobials, the drugs are still an important part of therapy for treating acne. Retinoids attack acne at its root by targeting the comedones, but antimicrobial therapy can help reduce inflammation, speeding up the clearing process. “If you use the antimicrobials, either a benzoyl peroxide or an antibiotic, they are going to add additional anti-inflammatory activity, and they’re going to kill the P. acnes’ organisms,” Dr. Wolf said. “You’re attacking as many as possible of the different mechanisms that lead to the development of acne. The topical retinoids are literally attacking the root because the microcomedo is the earliest step of the evolution of acne.” Dr. Wolf added that numerous studies have shown that combination therapy pairing topical retinoids with antimicrobials is more effective than antimicrobial therapy alone. One large study, he pointed out, showed that when adapalene was combined with agents such as topical clindamycin or oral doxycycline, there was a significant increase in anti-acne activity. Old News? In many ways, the “news” about the ability of topical retinoids to treat inflammatory acne is not news at all. Dr. Shalita, for example, pointed out that studies published in the early 1970s convincingly showed that topical retinoid therapy was effective in treating inflammatory acne. James J. Leyden, M.D., Emeritus Professor of Dermatology at the University of Pennsylvania School of Medicine, had a hand in many of those early studies. While the role of retinoids in treating acne may be old hat to him, he said that for many dermatologists, the idea of using the agents for inflammatory acne is still new. If studies have shown that topical retinoids so effectively treat acne for three-plus decades, why haven’t dermatologists embraced the therapy sooner? In large part, experts say, many physicians never got past the idea that topical retinoids can cause irritation. “The consensus was that some of the retinoids like tazarotene can be quite inflammatory,” explained Dr. Shear. “When you have something that is quite inflammatory, you don’t tend to think of it as potentially anti-inflammatory.” He admitted that he was surprised by some of the data on the efficacy of retinoids in acne the panel reviewed in drafting the recommendations. “You immediately think of antibiotics to try to calm down inflammation,” Dr. Shear said, “but the retinoid idea is a good one. I’ve found that it has changed the way I practice.” Dr. Leyden said that another trend — the emergence of topical antibiotics to treat acne — in large part eclipsed the role of retinoids. Topical antibiotics were so heavily promoted as go-to drugs to treat inflammatory acne that many physicians simply never gave retinoids a chance in patients with inflammatory acne. “We had the topical antibiotic people saying that if you have inflammatory acne, use this class of drug and don’t use retinoids,” Dr. Leyden explained. “The idea that you should use both drugs in all types of patients, which I had helped demonstrate in 1973, got lost in the shuffle. It’s one of the major reasons that something that is now considered a new concept is actually an old concept. Perhaps its time has finally come.” Dr. Shalita said he thinks of the new recommendations as not presenting new information, but instead “re-emphasizing” what many probably know but have not put into practice. He also noted that one common misconception that may be keeping some dermatologists from using topical retinoids is that some think that benzoyl peroxide is a comedolytic. While it’s true that antibacterials reduce comedones, he said, they don’t have a direct comedolytic action. Instead, they have an effect on cytokines, which can induce comedones. The net clinical effect is a modest reduction in non-inflammatory lesions. Irritation and Long-Term Maintenance Despite a solid body of evidence reaching back more than three decades and recommendations from a star-studded panel, there are questions about when — and if — dermatologists will embrace the therapy. Some, like Diane Berson, M.D., Assistant Professor of Dermatology at Cornell Medical College, are optimistic that more dermatologists will start using topical retinoids to treat all forms of acne. “I think that more dermatologists are beginning to accept and understand the notion that topical retinoids have anti-inflammatory properties,” she said, “and that you therefore do not have to wait until the inflammatory component is under control to add them to the regimen. You can start these drugs right away.” While the original generation of retinoids may have received a bad rap as irritating, there have been significant changes in the drugs that make many easy to use. “The newer generation of topical retinoids and newer formulations of older formulations are less irritating than the first generation,” Dr. Wolf explained. “This is very significant because irritation with the use of topical retinoids has been a problem in terms of patient compliance, because they would often cause redness and dryness and peeling and itching and burning and stinging of the skin.” Dr. Leyden took that view a step further, saying that while some patients will experience irritation, it’s not enough of an issue to keep dermatologists from prescribing topical retinoids. “There’s no question that there are some patients who have trouble with topical retinoids, even the modern-day cream formulations,” he said. “They’re a small percentage, but clearly they exist.” Most patients who experience any reaction, however, will experience much more minor — and temporary — effects. “There is a significant group of people who struggle for the first week or two,” Dr. Leyden said. “But if you understand that the drugs work, you can get patients to use them correctly, and they really are complementary to antibiotics.” Irritation from topical retinoids, he added, should not keep dermatologists from using the drugs. “The irritation that most people experience is not worth talking about,” Dr. Leyden explained. “You need to tell patients up front that they may have some trouble during the first week or so of treatment. You explain that if they have trouble during the first week or so to stop and use the drug every other day, to tiptoe into the water.” To be truly effective in treating acne, however, retinoids need to be used on an ongoing basis as part of a maintenance therapy. While maintenance therapy is an entrenched part of dermatology for conditions like eczema and psoriasis, experts say that many physicians take a somewhat different view of treating acne. “Many dermatologists over the years have had a tendency to treat acne until it clears up and resolves,” Dr. Wolf said, “and then essentially discontinue treatment until the patient has a flare-up. Now we are recommending strongly that once a patient has been brought under control by the combination therapy, the antimicrobial agents should be discontinued and the topical retinoids should be maintained for what can be a fairly significant period of time to prevent recurrences of the acne.” The rationale for prescribing a maintenance therapy of retinoids gets back to the mechanism through which retinoids clear up acne. “The theory behind that last recommendation is that topical retinoids act on the microcomedo as well as through their anti-inflammatory properties,” Dr. Wolf said. “They are clearly the most effective of our agents for eliminating microcomedones, and the microcomedo is the earliest step in the evolution of acne.” Dr. Wolf pointed to a German study that found while tretinoin helped reduce microcomedones significantly, microcomedones began to flare up again once the retinoids were discontinued. “The study suggests that if you don’t maintain the use of a topical retinoid, the microcomedones will form again and lead to other acne lesions.” The only problem with maintenance therapy is that it is often difficult to convince patients to continue treatment once their acne is cleared. If the physician takes the time to explain the benefit to patients, however, patients will achieve greater compliance with a maintenance program. Rethinking a Disease As a result, the recommendations call on physicians — and their patients — to essentially rethink the way they treat acne. “Dermatologists have to believe that this is beneficial,” Dr. Wolf said, “because they and their staff will have to take the time to tell patients why they want them to keep using one of these products even though their acne looks good.” Dr. Leyden acknowledged that using topical retinoids to treat inflammatory acne takes time, particularly during the initial visit. “You have to make sure that people understand,” he explained. “You can’t just write a couple of prescriptions and say goodbye. After that it’s pretty easy, but it does take some time up front, and time has become precious.” “For patients’ sake,” Dr. Berson said, “it’s better to have them using a therapy that will keep them clear instead of making them deal with treatment again. For both physicians and patients, maintenance is easier than having to treat again. “It’s analogous to eczema patients,” she continued. “We treat them with steroids, but when they’re clear, we explain to them that they need to keep their skin lubricated with a moisturizer to prevent the eczema from coming back instead of treating it every time it flares.” Still, Dr. Berson acknowledged that the pressures of modern practice may leave some dermatologists less than enthusiastic about taking time out of their busy schedule to educate patients — even if it does ultimately free up more of their time in the long run. “With managed care and the general craziness of practice, many physicians may find that it’s harder to spend more and more time with patients,” she said. “When you have to explain a treatment regimen to patients, it is more work.” And Dr. Shear said there will undoubtedly be caution on the part of dermatologists as they try what to them is a new approach. Some will prescribe retinoids to four or five patients and then carefully watch for results. “If nobody gets better,” he said, “some will say, ‘I don’t believe this works.’ It’s the same thing if you use a treatment and get irritation in the first three or four patients. It’s a lot harder to prescribe it to the fifth patient.” Dr. Wolf said that patients may also resist retinoids, in part because of cost: “People may tell you, ‘I spent $120 on this gel or cream and my face got red,’” he explained. “Maybe they were overzealous and didn’t follow the directions properly, but if you see that sort of inflammation, you’re going to be a little cautious.” Even Dr. Leyden acknowledged that unless dermatologists have seen the effects of topical retinoids on these patients first-hand, they may have difficulty believing that a simple shift in strategy can produce such dramatic results. But he also pointed to a challenge that is bigger than convincing dermatologists to use a “new” class of drugs to treat acne, and that is changing their mindset about the disease itself. “I think a lot of dermatologists don’t like to treat acne,” he said, “and that’s a shame, because it can be a tremendous source of satisfaction. You see kids who are social recluses and almost depressed really bloom when they receive treatment. And after you’ve been practicing long enough, some of those people bring their teenagers to you and tell you how important it was for them to get treated and get better.”
W hen the Journal of the American Academy of Dermatology published consensus recommendations on the treatment of acne just over a year ago, a number of experts hailed them as an approach that was long overdue. The recommendations, which were issued by the Global Alliance to Improve Outcomes in Acne and were published in a supplement to the JAAD that was sponsored by an educational grant from Galderma, called for a change in the way that many dermatologists treat inflammatory acne. What Did Top Acne Treatment Experts from Around the World Recommend? When discussing what they thought should be standard acne treatment protocols, the experts stressed the following key elements: 1. Dermatologists should use topical retinoids as a first-line therapy for all forms of mild to moderate acne, not just comedonal or non-inflammatory acne. 2. Combination therapy that includes a topical retinoid plus an antimicrobial is the most effective initial approach. Once control is achieved, they say, many patients can be maintained on topical retinoids as sole therapy. 3. While systemic antibiotics remain an important class of therapy, the recommendations call for dermatologists to use these drugs for as short a period of time as possible because of concerns about emerging resistance. The recommendations are supported by a substantial body of evidence from clinical trials. But dermatologists who participated in the conference that produced the recommendations also say that the recommendations raised questions about how many dermatologists around the world will change their longstanding behaviors when it comes to treating acne. Paradigm Shift For many dermatologists, using retinoids to treat inflammatory acne may seem counterintuitive. These drugs, after all, can potentially cause significant irritation in the initial course of treatment, so why use them on a patient who is already inflamed? The simple answer is that study after study has proven that topical retinoids, even as monotherapy, can clear patients with inflammatory acne or all types of acne effectively and keep the condition at bay more effectively than antibiotics alone. The recommendations point to the science — much of it 30 years old — showing that topical retinoids not only efficiently eliminate blackheads and whiteheads, but that they attack acne at the microcomedo level. As a result, they call on dermatologists to use topical retinoids as a first-line therapy to treat all forms of acne, not just comedonal forms of the disease. “We think that topical retinoids can be used alone for comedonal activity,” explained Alan R. Shalita, M.D., Professor and Chairman of Dermatology at the State University of New York and Downstate Medical Center in Brooklyn. “For inflammatory acne, many papers show that topical retinoids used with an antibacterial agent are more effective than the antibacterial agent alone.” John E. Wolf Jr., M.D., Professor and Chairman of the Department of Dermatology at Baylor College of Medicine, said that for many dermatologists, the recommendations will represent a “paradigm shift.” While the recommendations do not tell dermatologists to stop using antimicrobial therapies for acne, they do call on physicians to use antimicrobial therapies as second-tier therapies, and in conjunction with retinoids. Experts on the panel that produced the recommendations realize that they are contradicting the practice habits of many dermatologists. “We’re very comfortable with the idea of using antibiotics because they’re safe and effective,” explained Neil Shear, M.D., the Helen and Paul Phelan Professor of Dermatology and Chief of Dermatology at the University of Toronto Medical School. “But the whole idea of drug resistance because of antibiotic use is a real one with serious public health implications.” “One of the arguments for discontinuing antimicrobial therapies as soon as possible is that they may lead to antibiotic resistance,” explained Dr. Wolf. “One concern is that you may encourage resistance of Propionibacterium acnes. Another concern is that you may develop resistance to other bacteria like Staphylococcus aureus that are medically more significant than P. acnes alone.” “The consensus was that if you needed to use an antimicrobial on a long-term basis,” Dr. Wolf continued, "you should use a benzoyl peroxide product or that product in conjunction with antibiotics. In both cases, you’ve got less of a resistance issue. “With benzoyl peroxide,” he said, “there’s no evidence of antibiotic resistance. And with the combination of benzoyl peroxide and antibiotics, there’s less resistance than with antibiotics alone, and there’s no evidence of resistance induced by a topical retinoid.” While the recommendations call for less use of antimicrobials, the drugs are still an important part of therapy for treating acne. Retinoids attack acne at its root by targeting the comedones, but antimicrobial therapy can help reduce inflammation, speeding up the clearing process. “If you use the antimicrobials, either a benzoyl peroxide or an antibiotic, they are going to add additional anti-inflammatory activity, and they’re going to kill the P. acnes’ organisms,” Dr. Wolf said. “You’re attacking as many as possible of the different mechanisms that lead to the development of acne. The topical retinoids are literally attacking the root because the microcomedo is the earliest step of the evolution of acne.” Dr. Wolf added that numerous studies have shown that combination therapy pairing topical retinoids with antimicrobials is more effective than antimicrobial therapy alone. One large study, he pointed out, showed that when adapalene was combined with agents such as topical clindamycin or oral doxycycline, there was a significant increase in anti-acne activity. Old News? In many ways, the “news” about the ability of topical retinoids to treat inflammatory acne is not news at all. Dr. Shalita, for example, pointed out that studies published in the early 1970s convincingly showed that topical retinoid therapy was effective in treating inflammatory acne. James J. Leyden, M.D., Emeritus Professor of Dermatology at the University of Pennsylvania School of Medicine, had a hand in many of those early studies. While the role of retinoids in treating acne may be old hat to him, he said that for many dermatologists, the idea of using the agents for inflammatory acne is still new. If studies have shown that topical retinoids so effectively treat acne for three-plus decades, why haven’t dermatologists embraced the therapy sooner? In large part, experts say, many physicians never got past the idea that topical retinoids can cause irritation. “The consensus was that some of the retinoids like tazarotene can be quite inflammatory,” explained Dr. Shear. “When you have something that is quite inflammatory, you don’t tend to think of it as potentially anti-inflammatory.” He admitted that he was surprised by some of the data on the efficacy of retinoids in acne the panel reviewed in drafting the recommendations. “You immediately think of antibiotics to try to calm down inflammation,” Dr. Shear said, “but the retinoid idea is a good one. I’ve found that it has changed the way I practice.” Dr. Leyden said that another trend — the emergence of topical antibiotics to treat acne — in large part eclipsed the role of retinoids. Topical antibiotics were so heavily promoted as go-to drugs to treat inflammatory acne that many physicians simply never gave retinoids a chance in patients with inflammatory acne. “We had the topical antibiotic people saying that if you have inflammatory acne, use this class of drug and don’t use retinoids,” Dr. Leyden explained. “The idea that you should use both drugs in all types of patients, which I had helped demonstrate in 1973, got lost in the shuffle. It’s one of the major reasons that something that is now considered a new concept is actually an old concept. Perhaps its time has finally come.” Dr. Shalita said he thinks of the new recommendations as not presenting new information, but instead “re-emphasizing” what many probably know but have not put into practice. He also noted that one common misconception that may be keeping some dermatologists from using topical retinoids is that some think that benzoyl peroxide is a comedolytic. While it’s true that antibacterials reduce comedones, he said, they don’t have a direct comedolytic action. Instead, they have an effect on cytokines, which can induce comedones. The net clinical effect is a modest reduction in non-inflammatory lesions. Irritation and Long-Term Maintenance Despite a solid body of evidence reaching back more than three decades and recommendations from a star-studded panel, there are questions about when — and if — dermatologists will embrace the therapy. Some, like Diane Berson, M.D., Assistant Professor of Dermatology at Cornell Medical College, are optimistic that more dermatologists will start using topical retinoids to treat all forms of acne. “I think that more dermatologists are beginning to accept and understand the notion that topical retinoids have anti-inflammatory properties,” she said, “and that you therefore do not have to wait until the inflammatory component is under control to add them to the regimen. You can start these drugs right away.” While the original generation of retinoids may have received a bad rap as irritating, there have been significant changes in the drugs that make many easy to use. “The newer generation of topical retinoids and newer formulations of older formulations are less irritating than the first generation,” Dr. Wolf explained. “This is very significant because irritation with the use of topical retinoids has been a problem in terms of patient compliance, because they would often cause redness and dryness and peeling and itching and burning and stinging of the skin.” Dr. Leyden took that view a step further, saying that while some patients will experience irritation, it’s not enough of an issue to keep dermatologists from prescribing topical retinoids. “There’s no question that there are some patients who have trouble with topical retinoids, even the modern-day cream formulations,” he said. “They’re a small percentage, but clearly they exist.” Most patients who experience any reaction, however, will experience much more minor — and temporary — effects. “There is a significant group of people who struggle for the first week or two,” Dr. Leyden said. “But if you understand that the drugs work, you can get patients to use them correctly, and they really are complementary to antibiotics.” Irritation from topical retinoids, he added, should not keep dermatologists from using the drugs. “The irritation that most people experience is not worth talking about,” Dr. Leyden explained. “You need to tell patients up front that they may have some trouble during the first week or so of treatment. You explain that if they have trouble during the first week or so to stop and use the drug every other day, to tiptoe into the water.” To be truly effective in treating acne, however, retinoids need to be used on an ongoing basis as part of a maintenance therapy. While maintenance therapy is an entrenched part of dermatology for conditions like eczema and psoriasis, experts say that many physicians take a somewhat different view of treating acne. “Many dermatologists over the years have had a tendency to treat acne until it clears up and resolves,” Dr. Wolf said, “and then essentially discontinue treatment until the patient has a flare-up. Now we are recommending strongly that once a patient has been brought under control by the combination therapy, the antimicrobial agents should be discontinued and the topical retinoids should be maintained for what can be a fairly significant period of time to prevent recurrences of the acne.” The rationale for prescribing a maintenance therapy of retinoids gets back to the mechanism through which retinoids clear up acne. “The theory behind that last recommendation is that topical retinoids act on the microcomedo as well as through their anti-inflammatory properties,” Dr. Wolf said. “They are clearly the most effective of our agents for eliminating microcomedones, and the microcomedo is the earliest step in the evolution of acne.” Dr. Wolf pointed to a German study that found while tretinoin helped reduce microcomedones significantly, microcomedones began to flare up again once the retinoids were discontinued. “The study suggests that if you don’t maintain the use of a topical retinoid, the microcomedones will form again and lead to other acne lesions.” The only problem with maintenance therapy is that it is often difficult to convince patients to continue treatment once their acne is cleared. If the physician takes the time to explain the benefit to patients, however, patients will achieve greater compliance with a maintenance program. Rethinking a Disease As a result, the recommendations call on physicians — and their patients — to essentially rethink the way they treat acne. “Dermatologists have to believe that this is beneficial,” Dr. Wolf said, “because they and their staff will have to take the time to tell patients why they want them to keep using one of these products even though their acne looks good.” Dr. Leyden acknowledged that using topical retinoids to treat inflammatory acne takes time, particularly during the initial visit. “You have to make sure that people understand,” he explained. “You can’t just write a couple of prescriptions and say goodbye. After that it’s pretty easy, but it does take some time up front, and time has become precious.” “For patients’ sake,” Dr. Berson said, “it’s better to have them using a therapy that will keep them clear instead of making them deal with treatment again. For both physicians and patients, maintenance is easier than having to treat again. “It’s analogous to eczema patients,” she continued. “We treat them with steroids, but when they’re clear, we explain to them that they need to keep their skin lubricated with a moisturizer to prevent the eczema from coming back instead of treating it every time it flares.” Still, Dr. Berson acknowledged that the pressures of modern practice may leave some dermatologists less than enthusiastic about taking time out of their busy schedule to educate patients — even if it does ultimately free up more of their time in the long run. “With managed care and the general craziness of practice, many physicians may find that it’s harder to spend more and more time with patients,” she said. “When you have to explain a treatment regimen to patients, it is more work.” And Dr. Shear said there will undoubtedly be caution on the part of dermatologists as they try what to them is a new approach. Some will prescribe retinoids to four or five patients and then carefully watch for results. “If nobody gets better,” he said, “some will say, ‘I don’t believe this works.’ It’s the same thing if you use a treatment and get irritation in the first three or four patients. It’s a lot harder to prescribe it to the fifth patient.” Dr. Wolf said that patients may also resist retinoids, in part because of cost: “People may tell you, ‘I spent $120 on this gel or cream and my face got red,’” he explained. “Maybe they were overzealous and didn’t follow the directions properly, but if you see that sort of inflammation, you’re going to be a little cautious.” Even Dr. Leyden acknowledged that unless dermatologists have seen the effects of topical retinoids on these patients first-hand, they may have difficulty believing that a simple shift in strategy can produce such dramatic results. But he also pointed to a challenge that is bigger than convincing dermatologists to use a “new” class of drugs to treat acne, and that is changing their mindset about the disease itself. “I think a lot of dermatologists don’t like to treat acne,” he said, “and that’s a shame, because it can be a tremendous source of satisfaction. You see kids who are social recluses and almost depressed really bloom when they receive treatment. And after you’ve been practicing long enough, some of those people bring their teenagers to you and tell you how important it was for them to get treated and get better.”
