- Rosacea treatment shifts focus
- Related Content
- What is doxycycline?
- How does doxycycline help my acne?
- How long does it take to start working?
- How long do I need to take doxycycline?
- What’s the best way to take doxycycline?
- What are common side effects of doxycycline?
- Can doxycycline interact with any other medications?
- How much does doxycycline cost?
- What are some alternatives to doxycycline?
- Acne: Treatment With Antibiotics
- Topic Overview
- What is acne anyway?
- We need to change how we use antibiotics
- The future of acne treatment
- What Are the Pros and Cons of Treating Rosacea With Antibiotics?
- Efficacy of Extended-Release 45 mg Oral Minocycline and Extended-Release 45 mg Oral Minocycline Plus 15% Azelaic Acid in the Treatment of Acne Rosacea
Rosacea treatment shifts focus
Rosacea has always been challenging to treat, but continued research of late has forged a better understanding of the potential pathogeneses of the disease, with the common denominator appearing to be inflammation. Although more work needs to be done, this relatively new insight into rosacea has already opened the door for novel effective therapeutic approaches, bringing much needed relief to rosacea patients.
Much has been learned over the past decade about rosacea, but perhaps one of the most important pieces of the rosacea puzzle is that it is now understood to be a chronic inflammatory disorder; as such, the focus of treatment options has slowly shifted towards the anti-inflammatory and away from the antibiotic approach.
“We now know that rosacea is not an infectious disorder but a chronic inflammatory disorder, all of which leads to the concept that antibiotics are not the right way to go about treating it,” says Hilary E. Baldwin, M.D., Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, New York.
Although antibiotics are effective in the treatment of rosacea, they work by being anti-inflammatory agents. When full dose antibiotic agents are used, Dr. Baldwin says that more harm is ultimately caused than good, including the potential development of antibiotic resistances. According to Dr. Baldwin, the tetracycline class of antibiotics frequently used in rosacea is, in fact, a very good anti-inflammatory drug and in order to maximize the anti-inflammatory effect, lower doses of the antibiotic should be used.
“Recognizing that doxycycline has both anti-inflammatory and antibiotic capacities, we started playing around with anti-inflammatory dose doxycycline for the treatment of rosacea, and found a dose that was low enough not to be an antibiotic but high enough to impart a full anti-inflammatory ability. This was in part a kind of verification that rosacea indeed was a chronic inflammatory disease where there was an up-regulation of cathelicidins and matrix metalloproteinases in the epidermis that were suppressed by doxycycline,” Dr. Baldwin says.
Recommended: Facial erythema influences perceptions
There is an acute difference however between doxycycline (Oracea, Galderma), which is 40mg of doxycycline in a controlled dosing manner (and an anti-inflammatory dose), and low-dose antibiotics. At 40mg, doxycycline does not have antibiotic capabilities and therefore is not an antibiotic but instead an anti-inflammatory drug. According to Dr. Baldwin, 50mg/day doxycycline or minocycline, although effective in rosacea, are antibiotic doses, and low-dose at that. Antibiotic resistance is encouraged by inadequate dosing with antibiotics. Therefore, one could argue that 200mg/day is a less harmful dose than 50mg/day.
Q: I have a patient who has ocular/dermatologic rosacea with some severe corneal findings. His dermatologist prefers minocycline to doxycycline. Are there any real advantages or disadvantages of using one rather than the other?
A: The short answer: Both drugs have been proven effective at treating ocular rosacea, which mostly entails the same protocol as treating cutaneous rosacea. Still, doxycycline is considered preferable to minocycline for the treatment of rosacea, while minocycline is deemed the better of the two for treating acne.
But, the reasons behind these prescribing trends are more anecdotal and theoretical than based on large clinical trial. Except for a few small, decades-old studies that involved acne vulgaris patients, the two antibiotics have never been compared in a rigorous clinical trial. They evolved into their respective roles based on assumptions about their pharmacologic properties.
In the 1940s, physicians began looking for systemic ways to treat acne and gravitated toward antibiotics. They believed that the red, inflamed, pus-filled lesions were caused by bacterial infections. By the mid-1950s, tetracyclines were widely prescribed for acne; because they worked fairly well, no one questioned the mechanism of action.
Two tetracycline compoundsdoxycycline and minocyclinethat were introduced in the late 1960s and early 1970s, offered acne and rosacea patients easier dosing schedules and decreased side effects. Still, their antibiotic properties were considered operative.
In the 1980s, researchers discovered that these drugs work on acne, rosacea and related conditions, mainly through anti-inflammatory pathways. While investigating treatments for adult periodontitis, a 1983 animal study showed that minocycline inhibited tissue collagenolytic enzyme activity in ways independent of its antibacterial mechanism.1 This kicked off a whole new era in tetracycline research.
Anti-inflammatory mechanisms attributed to tetracyclines during this period include inhibition of matrix-degrading metalloproteinases (MMPs), proteolytic enzymes produced by infiltrating inflammatory cells and connective tissue cells in the periodontal matrix. Of the commercially available tetracyclines, doxycycline proved the best inhibitor of MMP activity.2 Also, doxycycline was best tolerated for long-term use.
As with any antibiotic, bacterial resistance is a worry. Although antimicrobial activity is not their primary purpose, tetracyclines are clearly associated with resistant strains of Propionibacterium acnes.3,4 P. acnes itself is not especially dangerous; however, microbes can pass resistance from one species to another.
So, minimizing resistance among all bacteria is prudent public health policy.5,6 Resistance was seen least often with minocycline, which is why it is widely indicated for acne. Bacteria do not directly cause acne, as once thought. Still, microbes do play a significant role in the disease, probably by inducing inflammatory immune response. Thus, some level of antimicrobial activity is considered beneficial.
In 1998, the FDA approved Periostat (doxycyline hyclate, CollaGenex Pharmaceuticals) for periodontal disease. (Some eye care practitioners prescribe Periostat off-label for ocular rosacea.) The dosage (20mg b.i.d.) is high enough to induce anti-inflammatory action but low enough to avoid antibacterial action and risk of bacterial resistance. Also, the lower dose minimizes side effects.
When Periostat went generic, CollaGenex re-introduced it as a 40mg, once-daily, time-released pill called Oracea, which gained FDA approval for treating rosacea in May 2006. Oracea is the drug of choice for rosacea, says Joseph Bikowski, M.D., assistant professor of dermatology at Ohio State University. However, the cost may be prohibitory. It is about $4 a pill. For that reason, some clinicians prescribe doxycycline off-label.
Minocycline is considered an acceptable second-line option, but there are more reports of adverse events than with doxycycline. Lightheadedness, loss of balance and dizziness may occur. Long-term use is associated with rare cases of a blue/black discoloration (sometimes permanent) of the sclera, teeth, skin and/or nails. Pneumonitis, lymphadenopathy, pseudotumor cerebri and an infectious mononucleosis-type reaction also have been reported.
There were reports of esophageal irritation with doxycycline hyclate, but a newer form of the drug, doxycycline monohydrate, which has a milder pH balance, seems to have solved this problem. A major concern with doxycycline is phototoxicity, a risk that appears to be dose dependent. Patients who fail to respond to standard doses may need to take up to 100mg or more per day; phototoxicity incidence increases to 3% for 100mg/day, 20% for 150mg/day and 42% for 200mg/day. All tetracyclines carry warnings of photosensitivity, but doxycycline has the highest risk of this side effect.
High-fat/high-protein foods, especially dairy products, and antacids can interfere with absorption of these drugs, so they should be taken one hour before or two hours after meals. Mineral supplements, such as aluminum, zinc, bismuth or magnesium, can have the same effect and should be avoided. A lot of older patients with macular degeneration will be taking zinc, so thats something to watch out for, says Bruce Onofrey, O.D., R.Ph., of Albuquerque, N.M.
Be warned: Breast cancer concerns may arise when discussing tetracyclines. A 2004 JAMA study generated headlines when it linked long-term antibiotic use to higher risk of breast cancer.7 Despite widespread publicity, the study did not establish causality. Periostat researchers investigated the issue prior to FDA approval and uncovered no direct carcinogenic effects.
1. Golub LM, Lee HM, Lehrer G, et al. Minocycline reduces gingival collagenolytic activity during diabetes. Preliminary observations and a proposed new mechanism of action. J Periodontal Res 1983 Sep;18(5):516-26.
3. Cooper AJ. Systematic review of Propionibacterium acnes resistance to systemic antibiotics. Med J Aust 1998 Sep 7;169(5):259-61.
5. Dahl MV. Pathogenesis of rosacea. Adv Dermatol 2001;17:29-45.
7. Velicer CM, Heckbert SR, Lampe JW, et al. Antibiotic use in relation to the risk of breast cancer. JAMA 2004 Feb 18;291(7):827-35.
Vol. No: 144:02Issue: 2/15/2007
Acne can be stubborn and frustrating to treat, and if you’ve been to the dermatologist, you may have heard of (or even been prescribed) doxycycline as part of a skincare regimen. Doxycycline is a popular treatment option, so let’s talk about what you should know while taking it.
What is doxycycline?
Doxycycline is an antibiotic, meaning it is a drug used to kill bacteria. It belongs to a group (sometimes called a “class”) of antibiotics known astetracyclines. Two other drugs in this class are tetracycline (yes it has the same name as the group!) and minocycline.
We don’t know for sure yet if any one of these three work better than the others, but your doctor will work with you to find the best treatment. Minocycline and doxycycline usually cause fewer side effects (like an upset stomach) and don’t have to be taken as often, so they are prescribed more commonly than tetracycline.
Brand names for doxycycline include Vibra-Tab, Doryx, and Oracea, among others. Generic versions includedoxycycline hyclate and doxycycline monohydrate.
How does doxycycline help my acne?
Bacteria live on everyone’s skin. In fact, there are around1,000 types of bacteria that call your skin home. One of them, called P. acnes, lives in the oil-producing glands of your skin. When you reach puberty, your testosterone levels will rise, causing those glands to make more oil. All that extra oil results in P. acnes multiplying and causing inflammation. Inflammation is one cause of acne.
Doxycycline treats acne by killing off these P. acnes bacteria, so they can’t cause inflammation, and also by reducing the inflammation that is already there.
How long does it take to start working?
Like other acne treatments, doxycycline needs some time to start working. Your acne might start improving within 2 weeks, but it can take up to 12 weeks (or 3 months) to see the full benefit of the treatment. You’ll know doxycycline is working for you when you see less acne forming and your skin starts to look clearer. Many treatments can make your skin look worse when you first start them, but this is generally not an issue with doxycycline.
How long do I need to take doxycycline?
If you’re still taking doxycycline at 3 months, you and your provider can decide whether or not you should continue taking it at that point. Doctors often limit doxycycline treatment to 3 months to prevent P. acnes from becomingresistant to doxycycline (meaning the medication no longer kills them). However, everyone is different, and your doctor might want you to stay on it longer.
Doctors also usually prescribe doxycycline with other treatments, primarily topical treatments like retinoid creams or benzoyl peroxide. This is so that:
- After you stop taking doxycycline, you still have treatment and your acne won’t come back
- You only need to take doxycycline for a short time (which reduces the chance that P. acnes will become resistant to doxycycline)
If your doctor prescribed doxycycline and another drug for you to use at the same time, it’s important to follow their instructions to get the best results.
What’s the best way to take doxycycline?
Doxycycline comes in a tablet or a capsule you take by mouth with a full glass of water. For acne, the typical dosing for doxycycline is 50 mg or 100 mg twice daily or 100 mg once daily. But some forms of doxycycline are taken as 20 mg twice daily or 40 mg once daily.
Doxycycline can cause an upset stomach, so if you experience this side effect, taking it with food can help. Keep in mind though some forms of doxycycline, like Oracea (doxycycline 40 mg), should be taken only on an empty stomach so your body can fully absorb it. Check with your doctor or pharmacist before starting treatment to find out how you should take it.
Dairy products and other foods as well as supplements high in calcium or iron can also prevent absorption. The key is to plan ahead. Don’t consume dairy products or take calcium or iron supplements within 1 hour before or 2 hours after taking doxycycline. Remember, too, that many multivitamins have iron and calcium in them that could interfere with your doxycycline treatment.
What are common side effects of doxycycline?
Most people do well on doxycycline, but all medications can cause side effects. The most common side effects of doxycycline are:
- Sun sensitivity (getting burned more easily in the sun). Be sure to protect yourself in the sun while taking doxycycline. If you’re planning to be outside, remember to wear sunscreen, find shady spots, and wear protective clothing, a hat, and sunglasses.
- Nausea, vomiting, or diarrhea. Depending on the type of doxycycline you have, your provider may recommend that you take it with food or switch to a different medication to avoid these side effects. Once you stop taking doxycycline, your stomach will likely feel better within a few days.
- Inflammation of your esophagus (the tube that connects your mouth to your stomach). This condition is known as esophagitis; it can feel like heartburn and might cause pain when you swallow. You can prevent esophagitis by not lying down for at least 30 minutes after taking doxycycline.
Rare side effects of doxycycline include:
- Permanent yellow staining of teeth. If children or pregnant women take doxycycline, it can permanently stain the children’s (or unborn child’s) teeth. Because of this, children and pregnant women shouldn’t take doxycycline for acne, though they may be able to take it for certain infections.
- Stevens-Johnson Syndrome (SJS) or toxic epidermal necrolysis (TEN). Both of these are very rare but serious immune reactions, usually caused by a medication. Symptoms start appearing 1 to 3 weeks after starting the medication and can include a rash, usually on the face, neck, or upper torso; fever; headache; and coughing. If you think you might be having these symptoms, call 9-1-1 or go to the nearest emergency room immediately. While SJS and TEN may be scary, keep in mind they are very rare. In fact, looking at all people (regardless of whether they’re taking a medication), it’s estimated that SJS happens in as few as 1 in 1 million people, and TEN happens in as few as 1 in 2 million people.
Always consult your provider if you have questions or concerns about side effects.
Can doxycycline interact with any other medications?
The following over-the-counter medications may make doxycycline less effective by blocking how much of it you absorb from your gut:
- Calcium-containing antacids (Tums)
- Iron supplements
- Bismuth subsalicylate (Pepto-Bismol, Kaopectate)
- Aluminum- and magnesium-containing products, like Milk of Magnesia, Maalox, and some multivitamins
These prescription medications can also interact with doxycycline:
- Warfarin. Warfarin is a popular blood thinner (a drug that keeps your blood from clotting). When taken with doxycycline, doxycycline can increase the effects of warfarin, leading to severe bleeding when your blood can’t clot properly. If you are taking warfarin, your provider will likely be monitoring your INR level, a measure of how much the warfarin is thinning your blood. This will be even more important if you start taking doxycycline.
- Seizure medications. Some seizure medications (phenytoin and phenobarbital, for example) might make your doxycycline less effective.
Note that this is not a complete list of all the medications and supplements that can interact with doxycycline. Make sure your doctor and pharmacist are aware of all the medications you are taking, including over-the-counter and herbal medications. That way they can check if doxycycline is safe for you.
How much does doxycycline cost?
Doxycycline hyclate and doxycycline monohydrate, the generic versions of doxycycline, are two forms that have similar effects and are prescribed at about the same rate.
However, the average retail price of doxycycline monohydrate is about half that of doxycycline hydrate. The average retail price for 20 capsules of 100 mg of doxycycline monohydrate is about $44, while the average retail price for the same prescription of doxycycline hydrate is about $87.
To save on doxycycline, check with your insurance plan first. Most Medicare plans and private insurance plans cover both doxycycline monohydrate and doxycycline hydrate. You can also save by usinga GoodRx coupon or a mail order pharmacy. Currently, the lowest GoodRx price for a prescription of twenty 100 mg tablets of either medication is just $12.
Regardless of whether your provider prescribes doxycycline hydrate or monohydrate to you, you can ask your pharmacist to swap your prescription for the other if you find that that price is better. They might just want to call your provider first to confirm it’s okay.
What are some alternatives to doxycycline?
Doxycycline is a popular acne medication, but it’s not for everyone. When it comes to antibiotics for acne, the American Academy of Dermatology also recommends these:
With all of the treatment recommendations out there for acne, don’t forget that your healthcare providers are there for you. Whether it’s sorting out side effects or figuring out your insurance coverage, work with your provider to find out which medication, if any, is right for you.
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Acne: Treatment With Antibiotics
Doctors often prescribe antibiotics to treat severe acne or acne that is likely to leave scars. Antibiotics improve the look of your skin by killing bacteria that cause acne. This means you’ll have fewer pimples and redness. Less acne means less acne scarring.
You can put antibiotics directly on your skin (topically) or take them by mouth (orally). Topical antibiotics kill bacteria on your skin. Oral antibiotics kill bacteria in your skin pores. Oral antibiotics work best if you start them at high doses. Your doctor will reduce the dose as your acne gets better.
People with mild acne may need only topical antibiotics. The most common types include:
- Clindamycin (such as Cleocin).
- Erythromycin (such as E-Mycin).
A topical antibiotic may be combined with a topical retinoid, such as tretinoin (Retin-A). Or a topical antibiotic may be combined with benzoyl peroxide gel.
Talk with your doctor before using these medicines if you are pregnant or breastfeeding.
People with severe acne and people who are more likely to have scarring from acne often take antibiotics by mouth. The most common oral antibiotics include:
If you are using topical antibiotics or taking oral antibiotics, your doctor also may have you use benzoyl peroxide on your skin. This can make it less likely that you will develop antibiotic resistance.
For more information on antibiotics, see Drug Reference. (Drug Reference is not available in all systems.)
Acne is one of the most common dermatologic diseases, affecting 40-50 million people each year in the United States. While best known as a bothersome part of puberty, affecting approximately 85 percent of young people, acne can persist (or even start) in adulthood, causing emotional and physical distress and sometimes permanent disfigurement.
Many people with acne will be prescribed antibiotics for treatment at some point. In fact, about five million prescriptions for oral antibiotics are written each year for the treatment of acne in the United States. While dermatologists comprise 1 percent of physicians overall, they are responsible for 5 percent of all antibiotic prescriptions written.
Even though national recommendations say that a course of antibiotics to treat acne shouldn’t last more than three months, a study published in the Journal of the American Academy of Dermatology found that the average amount of time a patient is prescribed an oral antibiotic is actually over 300 days.
Antibiotics may be prescribed at higher doses than what is really needed to treat acne. While antibiotics can kill the bacteria associated with acne, it’s their anti-inflammatory effects, not their antimicrobial effects, that yield the biggest skin-clearing benefits.
The result is that the bacteria associated with acne are becoming resistant to common antibiotics – and this overuse also contributes to more harmful bacteria, like Staphlycoccus aureus and Streptococcus becoming resistant.
What is it exactly? Practicalcures.com/Flickr, CC BY
What is acne anyway?
Acne is a chronic inflammatory skin condition, characterized by blackheads and whiteheads (called comedones), pimples, and deeper lumps (cysts or nodules). They are caused when hair follicles are clogged with oil, bacteria and dead skins cells, and can occur on the face, neck, chest, back, shoulders and upper arms.
Whiteheads, blackheads and pustules! Oh my! Acne diagram via www..com.
While once thought to be a direct result of overactive sebaceous oil glands, now we know that inflammation is the driving force behind acne. In fact, this inflammation can be seen in the skin even before a pimple pops up. And clogged follicles can also stimulate more inflammation.
The bacterium that lends its name to the condition Propionibacterium acnes, is just one of the factors that stimulates this acne-causing inflammation.
Hereditary and genetic factors, hormones, emotional stress and even diet can also bring on the zits. For instance, foods with a high glycemic load such as white grains (bread, rice, pasta) and sweets have been linked to acne, as they can increase oil production and skin cell turnover. This ultimately causes a backup in the pores and follicles on our skin – creating a nice environment for the inflammation-inducing P. acnes to flourish.
Treating the inflammation can help prevent acne from developing, and the potent anti-inflammatory effects of antibiotics can help to treat acne, much more than their ability to kill bacteria. For instance, the tetracycline class of antibiotics, such as doxycycline and minocycline, can inhibit the production of pro-inflammatory signaling molecules.
They also inhibit overactive demolition enzymes called matrix metalloproteinases. Normally, these enzymes help keep our skin healthy, breaking down old and dying structures to allow new ones to be built up. But when they’re overactive, these enzymes can damage the hair and oil gland unit as well as surrounding supporting structures in the skin.
When that happens, these enzymes contribute to the formation of the big, angry, red, cystic acne lesion, and they can also contribute to the creation of pitted scars.
This is why antibiotics are used to treat acne, but also rosacea, razor bumps and scarring hair loss, to name a few other dermatological conditions.
Antibiotics also have anti-inflammatory effects. Antibiotics image via www..om.
We need to change how we use antibiotics
Thanks to using higher-than-needed doses of antibiotics and keeping patients on them for longer than recommended, the P. acne and other skin bacteria, like Staphlyococcus aureus (MRSA, the multi-drug resistant strain of staph bacteria) have developed resistance to multiple topical and oral antibiotics used to treat this disease chronically. For instance, 20 or 30 years ago, the antibiotic erythromycin was used frequently to treat acne, but now both bacteria are uniformly resistant.
So far we have not seen too much resistance to the tetracycline class of antibiotics used today, but they too will be on their way out if we do not change our prescribing patterns.
This is frustrating because antibiotics don’t need to kill bacteria to treat acne. Clearing P. acnes from the area can be helpful, but the bacteria is just one stimulus of inflammation, so removing it is an assist, not a win. And research has shown that the desired anti-inflammatory effects can be achieved at sub-antibacterial dosing. This means that the needed dose is so low that it can’t kill good bacteria or challenge pathogenic bacteria to become resistant.
And antibiotics should never be prescribed on their own to treat acne. In fact, treatment guidelines always recommend that antibiotics be combined with a nonantibiotic topical treatment.
An oldie but goodie is benzoyl peroxide in a relatively low strength (2.5 percent, compared to the 8-10 percent that you get at the drugstore). It can kill P. acnes, but because it’s not an antibiotic, bacteria can’t become resistant to it. It can also break down the skin overgrowth covering the pore, which leads to blemishes.
Retinoids, derived from vitamin A, are by far the most effective topical anti-acne drugs. They limit pore clogging, inhibit inflammation and matrix metalloproteinases. Retinoids also affect the various genes involved in producing the structural components of the skin, such as collagen and elastin, improving the appearance of scars.
Better treatments on the horizon? Woman image via www..com.
The future of acne treatment
A future direction in acne treatment development is utilizing agents that can kill P. acnes but that don’t lead to microbial resistance.
For instance, there are studies using synthetic antimicrobial peptides, tiny strings of amino acids that can physically destroy P. acnes. This remedy would likely be used in conjunction with other therapies that can treat other causes of acne.
Even more promising is the use of nitric oxide, one of the most important and potent biological molecules, which can both kill P.acnes without the risk of it or any other bacteria developing resistance and inhibit multiple elements of inflammation involved in the formation of the vicious pimple. The limitation to date has been delivery, as nitric oxide is highly unstable.
But nanotechnology might provide a way of delivering nitric oxide to treat acne. I, along with collaborators at the Albert Einstein College of Medicine and the University of California, Los Angeles, have shown that a nanoparticle capable of generating low levels of nitric oxide over time could hit all the key pathologic elements that lead to acne.
In the meantime, if you are prescribed antibiotics for acne, ask your doctor how long you need to take them and if the dose is appropriate. And try to avoid popping those zits.
Newark, NJ—Dermatologists tend to prescribe a lot of antibiotics for conditions such as acne, but that might be changing.
A series of articles in the journal Dermatologic Clinics analyzed studies on acute and long-term acne treatments over the past decade to identify trends.
“Therapeutic actives for acne have changed little in the last decade. Recognition that acne is an inflammatory, not infectious condition has led to a call for reduction in antibiotic use,” conclude the study authors from the Rutgers University School of Medicine. “This has culminated in a re-evaluation of highly efficacious combination topical therapy, improved vehicle technology, and a renaissance for spironolactone and isotretinoin.”
Laser and light modalities, although not sufficiently studied for first-line use, show promise for the future.
The study points out that, in patients using topical and oral antibiotics:
• An increase of bacteria in the back of the throat and tonsils compared with nonusers to was three times more likely
• Long-term use of antibiotics in acne treatment is associated with an increase in upper respiratory infections and skin bacteria; and
• Glucose levels are affected by long-term antibiotic therapy.
“People are more conscious about the global health concern posed by the overuse of antibiotics and that acne is an inflammatory, not infectious, condition,” explains Hilary Baldwin, MD, clinical associate professor of dermatology at Rutgers’ Robert Wood Johnson Medical School. “Overuse of antibiotics also can promote the growth of resistant bacteria, which can make treating acne more challenging.”
To avoid those problems, Dr. Baldwin points out, interest has been renewed in an older drug, the antibacterial medication benzoyl peroxide, which often is used in combination with topical retinoids. A benefit, she notes, is that benzoyl peroxide kills acne-causing bacteria, helps the skin shed more effectively, reduces clogged pores, and does not promote resistant acne-inducing bacteria strains.
The study notes that acne often continues into adulthood, affecting about one-half of women in their 20s, one-third in their 30s, and one-fourth in their 40s. Among other possible treatments are spironolactone, which appears to be particularly effective in women; hormonal therapies that target androgens in the development of acne; laser and light therapies; and diet regulation.
The study authors suggest that, in severe acne, early intervention with the retinoid isotretinoin is effective without antibiotics. “This oral medication is unique among acne therapies in that it has the potential to not just treat acne but to eradicate it. It is 80 percent effective if a complete course is taken,” notes coauthor Justin Marson, a medical student at Robert Wood Johnson Medical School. “Studies also have disproven internet theories that the medication increases the risk of depression, ulcerative colitis and Crohn’s disease.”
Use of antibiotics is expected to continue at some level, however. The researchers emphasize that those medications are highly effective for moderate-to-severe cases of inflammatory acne and are approved by the FDA as a supplement to other treatments, such as benzoyl peroxide or a topical retinoid.
“Numerous studies have shown that these combinations are fast, effective and help reduce the development of resistant strains of bacteria that cause acne, but the CDC recommend that antibiotics be used for a maximum of six months,” Dr. Baldwin explains.
What Are the Pros and Cons of Treating Rosacea With Antibiotics?
Everyday Health: Are there situations when you would recommend antibiotics for rosacea treatment, or are you concerned about overuse and antibiotic resistance?
Jessica Wu, MD (drjessicawu.com)
For my patients with mild or early rosacea, I discuss lifestyle changes, with an emphasis on avoiding factors that trigger their symptoms. Many of my patients prefer to avoid antibiotics, and I’ve been impressed with how well some of them can control their symptoms by being strict and diligent with their food, skincare, and lifestyle choices. For those who need additional help, I may prescribe metronidazole gel (Metrogel) or azelaic acid gel (Finacea). If the flare-up if stubborn or sudden, I might recommend oral antibiotics including doxycycline or minocycline. I typically start with a low dose to take advantage of the anti-inflammatory effects of the antibiotic while minimizing the risk of side effects. I see patients in the office every three to four weeks to monitor their progress, and keep them at the minimum dose needed to control their symptoms. Once the symptoms subside, usually in a month or so, I taper them off the antibiotics. I explain to patients that the goal is to manage their flare-ups, not to stay on the antibiotics forever, since it’s not a real cure.
Nicholas Perricone, MD (perriconemd.com)
Systemic antibiotics would be low on my list of treatments for all of the obvious reasons.
Elizabeth Tanzi, MD (skinlaser.com)
I like to minimize my oral antibiotic use only for rosacea flare-ups — when there is an explosive breakout and inflammation. Otherwise, I like the combination of topical products and laser treatments.
Howard Murad, MD (murad.com)
The signs and symptoms of rosacea vary substantially from one patient to another, and treatment must be tailored for each individual case. For patients with redness and pimples, doctors often prescribe oral antibiotics such as tetracycline and topical therapy to bring the condition under immediate control, followed by long-term use of the topical therapy alone to maintain remission. When appropriate, laser treatment or other surgical procedures may be used to remove visible blood vessels, reduce extensive redness or correct disfigurement of the nose. Eye symptoms are commonly treated with oral antibiotics and ophthalmic therapy, but if left untreated, can lead to blindness.
Rosacea patients are advised to identify and avoid lifestyle and environmental factors that may aggravate their individual conditions. Patients may also benefit from gentle and appropriate skin care, and cosmetics may be used to reduce the effect of rosacea on appearance.
It is unknown exactly why antibiotics work against rosacea, but it is widely believed that it is due to their anti-inflammatory properties, rather than their bacteria-fighting capabilities. Treating your topical skincare needs, following a proper diet and identifying stress triggers that lead to flare ups, a three-pronged approach that I call “inclusive health,” will all help lessen the effects of rosacea.
Macrene Alexiades-Armenakas, MD (drmacrene.com)
Yes, in patients whose rosacea does not clear on topical treatment and lasers, antibiotics may be necessary for some time. Once clear, I wean patients off of antibiotics.
Dennis Gross, MD (dennisgrossmd.com)
Sometimes lifestyle changes and over-the-counter remedies are enough to keep rosacea at bay, so I would recommend that to a patient before antibiotics. However, if a patient has been adhering to a regimen for at least a month and has not seen visible results then I do recommend a prescription topical, oral antibiotics or light acid peels. Oral medications such as tetracycline, doxycycline, and minocycline, all have been proven to keep rosacea’s bacterial component under control and also seem to have an anti-inflammatory benefit. Topical products such as metronidazole and clindamycin work in much the same way. Light peels help to keep the skin antiseptic and combat bacteria.
Jeannette Graf, MD (askdrgraf.com)
I am always concerned about overusing antibiotics and antibiotic resistance; however, when indicated in rosacea they can be extremely helpful when topical treatment alone is ineffective. Situations where I recommend antibiotics include an acute flare-up of perioral dermatitis, a flare-up of inflammatory papules and pustules in spite of topical treatment, and ocular rosacea with blepharitis.
Neil Sadick, MD (sadickdermatology.com)
Typically, I would only recommend antibiotics in cases where a patient has inflammatory pustule lesions and significant redness. There is always a concern regarding overuse of antibiotics and resistance.
Marta Rendon, MD (drrendon.com)
Yes, in certain circumstances oral antibiotics are indicated to treat rosacea. Antibiotics are used in moderate to severe pustular rosacea. Often the dose of the antibiotics is a very low dose that is not effective as an antibiotic but is effective as an anti-inflammatory. Antibiotics are discontinued as soon as possible in order to limit any possible antibiotic resistance. The oral antibiotics are used along with topical medications in order to facilitate this.
H.L. Greenberg, MD (lasvegasdermatology.com)
Yes, if there is severe inflammation, I would recommend an antibiotic, be it a topical or pill form. Resistance is always an issue with antibiotic therapy; however, I would not let that issue dictate my therapy for an individual patient.
Sarah Swanson (sarahswansonskincare.com)
The initial management of rosacea should be topical: mild cleansers, avoidance of irritants, and topical antibiotics or benzoyl peroxide. We recommend topical metronidazole, usually our first-line agent, with or without benzoyl peroxide. This avoids the overuse of oral antibiotics and resistance. When patients fail initial therapy, topical retinoids and oral antibiotics are necessary. Tetracycline is the most common antibiotic used and when possible should be tapered after initial therapy and/or replaced by topical metronidazole to minimize the risks of antibiotic overuse.
Eric Schweiger, MD (nyccosmeticdermatology.com)
Antibiotic use can be very helpful for inflammatory and papular (bumpy) rosacea. I use them frequently for patients with deep red cheeks and acne-like lesions with success, as long as we limit the course of antibiotics in patients with rosacea to three months or under, or as long as we think it is safe and effective.
Nelson Lee Novick, MD (youngerlookingwithoutsurgery.com)
Yes, I am concerned about the overuse of antibiotics and the potential for bacterial resistance to antibiotics that may result from this. As a rule, I try to avoid oral antibiotics for most mild to moderately severe cases of rosacea. Topical therapies that include metronidazole cream or gel, azelaic acid cream or gel, and niacinamide can be quite effective in these instances. For more difficult cases, I usually do add an oral antibiotic. My favorite is Oracea, which is a tetracycline-derivative antibiotic that is given in sub-antibiotic doses. Given in this fashion, the medication works as an anti-inflammatory agent, that is, to suppress the inflammation and redness of rosacea acne, without leading to the problems or concerns engendered by the use of conventional antibiotics.
Darrell W. Gonzales, MD (coastaldermonline.com)
There are both topical and oral treatment options to help control and halt the process of rosacea, but there is some very reasonable concern that the overuse of these medications may lead to bacterial resistance. Ideally, it is best to treat rosacea with topical agents such as metronidazole and sodium sulfacetamide. These products work for many rosacea patients without the risk of developing antibiotic resistance. For patients with more persistent, pustular, or inflammatory rosacea, oral antibiotics are sometimes necessary and effective. One of the most common forms of oral antibiotics for the treatment of rosacea is doxycycline. Fortunately, there are newer formulations of doxycycline with concentrations that can treat rosacea without running the risk of antibacterial resistance. Persons with rosacea not responding to topical agents should ask their dermatologist about this special formulation of doxycycline.
Jeffrey Ellis, MD and Amy Slear, MD (belaray.com)
Many medications are available, and the key in treating the condition is to find a dermatologist who will be able to identify the best options for your individual situation. Options may include topical creams, oral antibiotics, or low dose Accutane. Each option has its own pros and cons that need to be carefully considered on an individual basis.
William Ting, MD (drwilliamting.com)
Oral antibiotics may be indicated for inflammatory acne rosacea, particularly with formation of puss bumps. Recent introduction of submicrobial doxycycline minimizes risks of antibiotic resistance.
Dina Strachan, MD (dinastrachanmd.com)
Yes, I do recommed use of antibiotics for some patients and yes, I am concerned about antibiotic resistance. The good news is that rosacea is not caused by bacteria, so you don’t need a truly “antibiotic” dose of a drug such as doxycycline, to treat rosacea — a lower, antiinflammatory dose will do. This is called a subantimicrobial dose.
Brad Abrams, DO (abramsderm.com)
Antibiotics are commonly recommended for the treatment of rosacea. However, once facial veins have appeared on the surface of the skin more efficient treatment are available. Because antibiotic resistance is a concern, I always suggest a laser treatment alleviate the use of drug. Patients have seen amazing results with the laser treatment for rosacea.
Eric Huang, MD (plasticsandderm.com)
Moderate to severe rosacea patients may have papules, pustules, and phymatous changes, all of which can have a significant impact on patients’ lives. Some patients will limit social and professional activities due to embarrassment and low self-esteem concerning their appearance, thus the emotional and psychological impact of rosacea is important to acknowledge. Further, ocular involvement may occur in up to 50 percent of patients and may lead to iritis, corneal neovascularization, and scarring. Thus, despite the rightful concern over antibiotic overuse and resistance, I believe oral antibiotics play an important role in the treatment of rosacea patients.
Rosacea, which is characterized by redness of the face, blushing, acne-like eruptions, and more, has several different treatment options based on the type of rosacea present. Return to normal skin is the primary treatment goal.
Rosacea—the disease that turns of an innocent blush into a raging flush on the convex areas of the face—is relapsing, remitting, and progressive. Its inflammation chronically affects up to 10% of the population. 1 Rosacea usually begins in adulthood with symptoms of sensitive skin, increased flushing, burning, and itching. Acne-like eruptions (papules, pustules, and erythematous plaques) may develop, although they are less likely to appear in darker-skinned people than in fair-skinned individuals.
With time, telangiectasias (arteriovenous malformations causing “spider veins”), ocular manifestations, dryness, and phymatous changes may develop. 2,3 Some patients develop symptoms on their necks, upper chests, and scalps; this type of rosacea is probably associated with sun exposure and damage. 4 A number of triggers have been associated with rosacea.5-7
Rosacea’s causes are poorly understood, but involve an inflammation in the vasculature and pilosebaceous units. In addition to its other symptoms, it leaves the skin sensitive to many topical agents and cosmetics.
Subtypes and Variants
• Erythematotelangiectatic rosacea (ETR) is associated with facial flushing for more than 10 minutes after exposure to stimuli. Common stimuli include emotional stress, hot drinks, spicy foods, exercise, alcoholic intake, and temperature changes.5-7 ETR’s erythema is most intense in the central portions of the face and absent in periocular areas. These patients generally find that many topical substances irritate, burn, or cause itching. Their skin is usually drier than the skin of other subtypes.
• Papulopustular rosacea, usually seen in middle-aged women, presents with central-facial erythema with overlying papules and pinpoint pustules. Flushing may also be present.
• Phymatous rosacea is characterized by the presence of phymata (solitary, coalescent lumps or benign growths) and marked skin thickening, especially on the nose (rhinophyma). Phymata can also develop on the chin, forehead, ears, or eyelids. In this type of rosacea, surgery is often necessary.8,9
• Ocular rosacea presents as a burning or itching sensation. Patients may be sensitive to light or feel like something is in their eyes. Blepharitis and conjunctivitis can co-occur and may eventually progress to keratitis, scleritis, or iritis.
• Among the less common variants are rosacea fulminans, granulomatous rosacea, and steroid rosacea. A severe form, rosacea fulminans presents with papules, nodules, and discharging cysts, and is sometimes associated with inflammatory bowel disease. Granulomatous rosacea, more prevalent in African Americans, generates firm nodules similar to those seen in cutaneous sarcoidosis and tuberculosis. Chronic use of topical steroids can also lead to rosacea. Steroids can improve rosacea’s signs and symptoms temporarily, but symptoms flare when topical steroids are withdrawn, creating a vicious cycle.1
Rosacea can be confused with acne vulgaris; telangiectasias are rosacea’s distinguishing feature. Seborrheic dermatitis often presents like rosacea, but unlike rosacea, it affects the periocular areas and may include greasy scaling. Other conditions that may be confused with rosacea are contact dermatitis, photodermatitis, and systemic diseases associated with facial flushing or eruption (like polycythemia vera, mastocytosis, superior vena cava syndrome, carcinoid syndrome, systemic lupus erythematosus, dermatomyositis, and mixed connective tissue disease).1
Rosacea is currently incurable, and treatment success is measured as reduction in erythema and inflammatory lesions; decrease in the number, duration, and intensity of flares; and reduced itching, burning, and tenderness.
Clinicians prescribe numerous topical antibiotics for rosacea (used primarily for their anti-inflammatory effects), azelaic acid, pimecrolimus, sulfacetamide sulfur, antiparasitics, and alphaagonists.
Metronidazole, the topical antibiotic/ anti-infective agent, is used most often and is generally well-tolerated. Topical clindamycin, erythromycin, and combination benzoyl peroxide-clindamycin may also be used, but are not FDAapproved for rosacea.10-12
Azelaic acid is a newer treatment. Its efficacy appears to be significantly greater than that of metronidazole for erythema and inflammation, but patients often find it irritating to the skin.13-15 The topical immunomodulators pimecrolimus and tacrolimus are being used, and pimecrolimus cleared rosacea in 50% of study subjects after 6 weeks in its pivotal trial, but another study could not replicate the findings.16,17 Both agents may produce a rare syndrome similar to steroid-induced acne.18
Some patients report improvement using the topical vitamin A retinoids adapalene and retinaldehyde. Because the retinoids work at the retinoic acid receptor, which affects keratinocyte proliferation, cell differentiation, and inflammation,19,20 these creams theoretically treat rosacea’s underlying causes, but more study is needed. A small study demonstrating that topical vitamin C possesses efficacy suggests that free radical production may contribute to inflammation.21
Erythema and flushing may be related to abnormalities in specific alpha-receptor genotypes. This suggests that topical alpha-agonist agents may help. The alpha-agonist oxymetazoline has been reported to reduce flares and inflammation in 2 case reports of patients with medication-resistant ETR.22
Some researchers have suggested that demodex folliculorum infection may lead to rosacea’s underlying inflammation.3 The antiparasitic drugs ivermectin and lindane, given orally, have shown some efficacy. Topical permethrin and crotamiton eradicate demodex folliculorum poorly, but may resolve some underlying inflammation.3
Tetracycline, doxycycline, and minocycline are the mainstay of oral treatment for rosacea.23 Azithromycin has also been beneficial and may be tolerated better than the tetracyclines when dosed 3 times a week.24,25 Based primarily on circumstantial evidence, some researchers have linked Helicobacter pylori to rosacea and used “triple therapy” (omeprazole and 2 of the following antibiotics: clarithromycin, amoxicillin, or metronidazole) successfully.26 Penicillin, erythromycin, amoxicillin, ampicillin, dapsone, and metronidazole have also been used orally when patients are resistant to or cannot use topical therapies and tetracyclines are contraindicated.27-31 Concurrent topical and oral antibiotics can be effective. Topical metronidazole 1% and oral doxycycline have been shown to be well-tolerated and to decrease lesion counts.32
Isotretinoin has strong anti-inflammatory effects and is particularly effective in younger adults and mild disease. It has also been shown to reduce phymatous changes.32 Other oral therapies that have been tried with varying degrees of success include spironolactone, prednisone, beta-blockers, ondansetron, and cyclooxygenase-2 inhibitors.33-35
Medication adherence is essential in this chronic disease, and pharmacists need to coach patients with rosacea to adhere closely to their therapy. Patients should be told about the importance of avoiding various types of makeup, as well as abstinence from alcohol, if either of those were factors in their particular disease processes.
Phototherapy or laser therapy has been shown to be useful for rosacea, reducing erythema and telangiectasias associated with rosacea.36,37 Restoration of normal skin, while not always possible, is a primary treatment goal. Patients need constant reminders about behavioral interventions, especially avoiding sun exposure and using sunscreen at all times. Avoiding triggers is also crucial, although it can be difficult for many patients. Patients should also identify and use moisturizers that feel comfortable on their skin.38 Kinetin, a plant cytokinin, has been shown to help restore the skin’s barrier and is available over-thecounter as a 0.1% lotion.39
Rosacea patients are often caught between the rock—needing topical medication to alleviate their distress— and the hard place—having skin that is so sensitive, many products cause more discomfort than they can tolerate. In this disease, as in so many others, patients may have to explore several treatment options before they find relief. Pharmacists should be aware that rosacea can be psychologically distressing, and complete relief may not be possible. â–
Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. The views expressed are those of the author and not those of any government agency.
1. Scheinfeld NS. Rosacea. Skinmed. 2006;5(4):191-194.
2. Halder RM, Brooks HL, Callender VD. Acne in ethnic skin. Dermatol Clin. 2003;21(4):609-615.
3. Callender VD. Acne in ethnic skin: special considerations for therapy. Dermatol Ther. 2004;17(12):184-195.
4. Scheinfeld N, Berk T. A review of the diagnosis and treatment of rosacea. Postgrad Med. 2010;122(1):139-143.
5. Wilkin JK. Oral thermal-induced flushing in erythematotelangiectatic rosacea. J Invest Dermatol. 1981;76(1):15-18.
6. Higgins E, du Vivier A. Alcohol intake and other skin disorders. Clin Dermatol. 1999;17(4):437-441.
7. Greaves MW, Burova BE. Flushing: causes, investigation and clinical consequences. J Eur Acad Dermatol Venereol. 1997;8(2):91-100.
8. Bogetti P, Boltri M, Spagnoli G, Dolcet M. Surgical treatment of rhinophyma: a comparison of techniques. Aesthetic Plast Surg. 2002;26(1):57-60.
9. Sadick H, Goepel B, Bersch C, Goessler U, Hoermann K, Riedel F. Rhinophyma: diagnosis and treatment options for a disfiguring tumor of the nose. Ann Plast Surg. 2008;61(1):114-120.
10. Dahl MV, Katz HI, Krueger GG, et al. Topical metronidazole maintains remissions of rosacea. Arch Dermatol. 1998;134:679–683.
11. Bjerke JR, Nyfors A, Austad J, Rajka G. Metronidazole (Elyzol) 1% cream vs placebo cream in the treatment of rosacea. Clin Trials J. 1989;26:187–194.
12. Breneman DL, Stewart D, Hevia O, Hino PD, Drake LA. A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. Cutis. 1998;61(1):44-47.
13. Colón LE, Johnson LA, Gottschalk RW. Cumulative irritation potential among metronidazole gel 1%, metronidazole gel 0.75%, and azelaic acid gel 15%. Cutis. 2007;79(4):317-321.
14. Elewski BE, Fleischer AB Jr, Pariser DM. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. Arch Dermatol. 2003;139(11):1444-1450.
15. Maddin S. A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea.J Am Acad Dermatol. 1999;40(6 pt 1):961-965.
16. Weissenbacher S, Merkl J, Hildebrandt B, et al. Pimecrolimus cream 1% for papulopustular rosacea: a randomized vehicle-controlled double-blind trial. Br J Dermatol. 2007;156(4):728-732.
17. Chu CY. An open-label pilot study to evaluate the safety and efficacy of topically applied pimecrolimus cream for the treatment of steroid-induced rosacea-like eruption. J Eur Acad Dermatol Venereol. 2007;21(4):484-490.
18. Bernard LA, Cunningham BB, Al-Suwaidan S, Friedlander SF, Eichenfield LF. A rosacea-like granulomatous eruption in a patient using tacrolimus ointment for atopic dermatitis. Arch Dermatol. 2003;139(2):229-231.
19. Del Rosso JQ. Acne and rosacea. J Drugs Dermatol. 2008;7(6):525.
20. Bikowski JB. Mechanisms of the comedolytic and anti-inflammatory properties of topical retinoids. J Drugs Dermatol. 2005;4(1):41-47.
21. Carlin RB. Topical vitamin C preparation reduces erythema of rosacea. Cosmetic Dermatology. 2001;35-38.
22. Shanler SD, Ondo AL. Successful treatment of the erythema and flushing of rosacea using a topically applied selective alpha1-adrenergic receptor agonist, oxymetazoline. Arch Dermatol. 2007;143(11):1369-1371.
23. Theobald K, Bradshaw M, Leyden J. Anti-inflammatory dose doxycycline (40 mg controlled-release) confers maximum anti-inflammatory efficacy in rosacea. Skinmed. 2007;6(5):221-226.
24. Bakar O, Demirçay Z, Yuksel M, Haklar G, Sanisoglu Y. The effect of azithromycin on reactive oxygen species in rosacea. Clin Exp Dermatol. 2007;32(2):197-200.
25. Fernandez-Obregon A, Patton DL. The role of Chlamydia pneumoniae in the etiology of acne rosacea: response to the use of oral azithromycin. Cutis. 2007;79(2):163-167.
26. Rebora A. The management of rosacea. Am J Clin Dermatol. 2002;3(7):489-496.
27. Torresani C, Pavesi A, Manara GC. Clarithromycin versus doxycycline in the treatment of rosacea.Int J Dermatol. 1997;36(12):942-946.
28. Bakar O, Demirçay Z, Gürbüz O. Therapeutic potential of azithromycin in rosacea. Int J Dermatol. 2004;43(2):151-154.
29. Pye RJ, Burton JL. Treatment of rosacea by metronidazole. Lancet. 1976;1(7971):1211-1212.
30. Saihan EM, Burton JL. A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea. Br J Dermatol. 1980;102(4):443-445.
31. Krause MH, Torricelli R, Kündig T, Trüeb RM, Hafner J. Dapsone in granulomatous rosacea. Hautarzt. 1997;48(4):246-248.
32. Fowler JF Jr. Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, usp monohydrate controlled-release capsules) and metronidazole topical gel 1% in the treatment of rosacea. J Drugs Dermatol. 2007;6(6):641-645.
33. Pelle MT, Crawford GH, James WD. Rosacea: II. Therapy. J Am Acad Dermatol. 2004;51(4):499-512; quiz 513-514.
34. Aizawa H, Niimura M. Oral spironolactone therapy in male patients with rosacea. J Dermatol. 1992;19(5):293-297.
35. Spirov G, Berova N, Vassilev D. Effect of oral inhibitors of ovulation in treatment of rosacea and dermatitis perioralis in women. Australas J Dermatol. 1971;12(3):149-154.
36. Larson AA, Goldman MP. Recalcitrant rosacea successfully treated with multiplexed pulsed dye laser. J Drugs Dermatol. 2007;6(8):843-845.
37. Kawana S, Ochiai H, Tachihara R. Objective evaluation of the effect of intense pulsed light on rosacea and solar lentigines by spectrophotometric analysis of skin color. Dermatol Surg. 2007;33(4):449-454.
38. Laqueize S, Czernieleski J, Baltas E. Beneficial use of Cetaphil moisturizing cream as part of a daily skin care regimen for individuals with rosacea. J Dermatol Treat. 2007;18(3):158-162.
39. Wu JJ, Weinstein GD, Kricorian GJ, Kormeili T, McCullough JL. Topical kinetin 0.1% lotion for improving the signs and symptoms of rosacea. Clin Exp Dermatol. 2007;32(6):693-695.
Efficacy of Extended-Release 45 mg Oral Minocycline and Extended-Release 45 mg Oral Minocycline Plus 15% Azelaic Acid in the Treatment of Acne Rosacea
It has been well documented that rosacea is an inflammatory response to local factors and not an infectious disease.3,5 It is important to utilize an agent that does not affect antimicrobial resistance while also impacting the disease. There are a variety of topical medications approved for the treatment of rosacea, but currently there is only one oral medication approved by the US Food and Drug Administration for the treatment of papulopustular rosacea, a subantimicrobial dose of doxycycline. Its effect has been demonstrated beyond its antimicrobial effects and may be more related to its anti-inflammatory capabilities, including but not limited to protease inhibtion.10 There are other oral agents utilized for the treatment of rosacea, including minocyline, tetracycline, sulfa-based antibiotics, and macrolides. Extended-release (ER) minocycline was formulated to avoid many of the side effects noted with high-dose minocycline. ER minocycline is produced in a variety of doses for use in acne, and dosing is based on weight. At the time of this study, the lowest available dose of ER minocycline, 45 mg, was delivered as a once-daily oral tablet.11,12 The reasoning behind this study was to demonstrate the efficacy of the lowest possible dose utilizing the anti-inflammatory effects of minocycline in the treatment of patients with papulopustular rosacea, while avoiding the impact and side effects of high-dose minocycline (100-200 g/day). Azelaic acid has been utilized in the treatment of rosacea and was used topically once daily in the comparison group.13,14 The objective of this study was to evaluate the safety, efficacy, and tolerability of ER 45 mg oral minocycline as monotherapy or combined with azelaic acid 15% in the treatment of rosacea.