A dermatology veteran with more than 40 years experience, Dr. Bikowski has a special interest in acne, which he has demonstrated by his numerous publications. In this interview he answers questions about acne, sharing clinical pearls, myths, as well as little known information about acne treatment.
Q: If you look at many acne studies, results are seen generally sooner than we see them clinically. Why do you think this happens?
Dr. Bikowski: If you look at any study of acne and rosacea, you will find that in the first four weeks there is a dramatic decrease in disease symptoms. You then will find that from week four to 12 the rate of improvement becomes much less than in the first four weeks. In reality what probably happens is the lesion counts, which are done by humans, are slightly inflated to begin with. Let’s say the inclusion criteria for a study is to have 20 lesions; It is not unusual—and the investigators will tell you this in private—that if a participant has only 18 or 19 lesions found, the investigator might order a recount with the “intention” of increasing the count to 20 lesions so they qualify for the study. So this large initial drop is not real. Every study that counts lesions should be a 16-week study where the first four weeks do not count and the rest do.
Q: Are there things most people don’t know about the tetracycline class of medications?
Dr. Bikowski: Tetracycline HCL is not a photosensitizer. There is not one single study in the literature that shows that. The warning is a class warning. In the late 60’s, they took a bunch of medical students and gave them demethylchlortetracycline, an entirely different molecule, put them on a fishing boat off the Florida Keys from 12 noon to 4 pm, and nine out of 10 of them sunburned. That then became a class warning for all tetracycline drugs.
•Don’t have patients stop doxycycline when going on vacation for a week or two. It takes four to six weeks to get good results for acne; we have to assume that is how long it takes to reach therapeutic levels in your skin. Therefore, we must assume that it takes a prolonged period to leave the skin.
•Don’t view isotretinoin as a “medication of last resort.”
•Clinically topical retinoids do not seem to be associated with increased photosensitivity. The association may derive from early study protocls.
Doxycycline is a photosensitizer, and the effect is dose-related. The photosensitization is usually not blocked by the use of sunscreen. Minocycline is not a photosensitizer. I use a lot of doxycycline, and my experience with doxycycline is that only one or two patients have had a photosensitive reaction to it. So if your patient is going on vacation for a week or two it doesn’t make sense to have them stop their doxycycline. Since it takes four to six weeks to get good results for acne, we have to assume that is how long it takes to reach therapeutic levels in your skin. Therefore, we must assume that it takes a prolonged period to leave the skin. Hence, if you stop it before you go on your vacation, it will still be in your skin most likely.
There is only one study—done on rats—on the anti-inflammatory effects of doxycycline vs. minocycline, but it shows that doxycycline is two to three times more anti-inflammatory than minocycline. Doxycycline is my drug of choice, because 40mg delayed release doxycycline (Oracea) has anti-inflammatory properties but no antibiotic properties. In my opinion, because there are no concerns about antibiotic resistance, it is the safer drug. In my clinical experience I have seen results with the 40mg doxycycline delayed release as good as higher doses. No head-to-head studies between doxycycline and minocycline have been done.
Q: If there is a patient who is getting good results from a regimen that includes doxycycline but cannot get off it without flaring, does not want to consider isotretinoin, and will be having acne for many more years, will you continue with doxycycline long-term? Do you have any concerns about its long-term safety?
Dr. Bikowski: We have been using the tetracycline class of systemic antibiotics to treat acne since the 50s and have never been able to prove that the use of these antibiotics over a prolonged time produces any medical problems. If the patient wants to stay on it I have no problem with that. I would try to get them to 40mg a day but I have had patients on 100mg a day for years without complications. If someone is happy with antibiotic/conventional therapy I would never force isotretinoin upon them even though I know that to be a better and safer drug.
Q: Do you have any tips from your long experience prescribing isotretinoin?
Dr. Bikowski: I let all patients know that isotretinoin is the safest, most effective treatment we have for acne and that isotretinoin is actually a normal chemical constituent of the human body. The i-Pledge program’s stress on two forms of contraception makes little sense, because in practice 80 percent of women taking isotretinoin don’t use a second form of birth control. The most popular form of birth control is the birth control pill. If it is taken daily without missing a dose, there is still a 0.3% chance of conception; with typical use, there is an eight percent chance of pregnancy per year. The only way to be 100 percent certain to avoid pregnancy and the complications associated with it is abstinence. Therefore, I do not give this medication to any woman who does not agree to sexual abstinence, even if she is using forms of birth control like IUDs. In the government’s most recent analysis of patients who got pregnant while taking isotretinoin, 80 percent reported using two forms of birth control and only 20 percent of those pregnancies were for women who declared abstinence. Therefore it appears that abstinence is the best choice.
Isotretinoin is a unique medication, as I have never seen it fail to clear acne. Studies from Europe that a minimum dose is 120-150mg/kg body weight total dose. I have a very simple dosing strategy to accomplish this. By taking two 30mg tablets once a day with food. At a dose of 60mg a day there are few adverse events. The minimum total dose is 120mg/kg of body weight. The total number of days to accomplish this is the exact weight of the patient in pounds. Therefore, if the patient weighs140 lbs. and takes 60mg/kg day for 140 days they will reach the minimum total dose of 120mg/kg body weight. You certainly may use the medication longer if desired or needed.
Many patient and some providers think that isotretinoin is “hard on the liver.” I have never seen a steep rise in LFTs or any liver complications in over 30 years. A rare patient may have a double in LFTs but never higher.
I obtain fasting baseline lipids and liver function tests and repeat in one month. If results are normal at one month I do not repeat until the last month of treatment. Studies show that those liver and lipid numbers will remain normal throughout the remainder of therapy, unless the dosage is increased. I repeat the levels the last month to prove they are still normal. I am not concerned about elevated lipids, i.e., triglycerides unless they get above 300, then order a low-fat diet and may decrease the dose of isotretinoin. I have never had to stop anybody because of elevated triglycerides.
Q: You often hear patients and dermatologists say that isotretinoin is a “medication of last resort.” I have seen patients prescribed multiple antibiotics as well as topicals with one being no more effective than the other continuing on for months or even years before considering isotretinoin. Do you think this makes sense?
Dr. Bikowski: No it doesn’t. And you see this mostly with the younger generation of dermatologists who may not be as familiar with the use of this drug in acne as those of us who have been around for a long period of time. It is my opinion that teaching of the diagnosis and treatment of acne in residency has decreased in the last 10 to 15 years.
Q: What is the difference between the different topical retinoids?
Dr. Bikowski: The honest answer is we don’t really know. I have been on many advisory boards and there are no studies to prove that one is definitively better than the other. I personally have seen very few instances of retinoid dermatitis from any of the three. Adapalene theoretically is put into a base that takes the retinoid molecule right down into the upper infundibulum where it’s supposed to go. If you prescribe skincare for the acne patient that includes just a cleanser and moisturizer and stop everything else applied to the skin except the retinoid, rarely is there retinoid dermatitis.
I tell patients with every retinoid to apply it every other day for two weeks, then titrate to every day. Tazorotene theoretically is supposed to be better for comedones, but there is no conclusive evidence.
Tretinoin is inactivated by sunlight, as we discovered in an interesting way. This information comes directly from speaking to Dr. James Leyden and Dr. Albert Kligman, based on a study done at the University of Pennsylvania. Tretinoin was originally used in an alcohol solution, which made people very dry but worked well. Six months later it stopped working. They realized that, although the original bottles were brown, after six months the pharmacist switched to clear bottles and the solution became photoinactivated.
Clinically I have not witnessed increased photosensitivity from any topical retinoids. When tretinoin was first put on the market in 1972, studies were not of the quality of studies done today; a lot of myths were passed on. I think if you were to do a true double-blind controlled study today there would be little to no photosensitivity. The package insert for tretinoin states that patients should wait 20 minutes after washing before applying tretinoin for concern that the hydrated skin would increase absorption too much and lead to irritation. This was simply a concern of the investigators shared with the FDA, and there were no studies to show that to be true. You would have to soak the skin in water for probably at least five minutes before the stratum corneum would become hydrated enough to increase penetration of topical medications.
Q: How often have you found cases of Pityrosporum (Malasezzia) folliculitis?
Dr. Bikowski: In my experience, about 90 percent of all teenagers have acne in combination with Pityrosporum folliculitis. Almost every teenager has Pityrosporum to some degree. Besides the normal areas on the forehead, nose, cheeks and chin, chest, shoulders, and back, it can also go up into the scalp, where acne is not normally found. It can also mimic seborrheic dermatitis except with more pustules. Almost every patient who comes in for acne I also treat for Pityrosporum folliculitis. I use ketoconazole shampoo on the scalp and face, as well as diflucan 200mg once a day for three days then once a week for three weeks. I re-examine in one month.
Q: Do you prescribe birth control pills for acne treatment?
Dr. Bikowski: I believe that we have medications that work faster and safer and are better than birth control pills therefore I do not prescribe them. n
Steven Leon, MS, PA-C works at Advanced Dermatology in Palmdale, CA.