Erythromycin

Let's talk quickly about erythromycin, I don't use much of it orally anymore either, it's the same dose. The advantages are that you can take it with food, but you can also take doxycycline and minocycline with food, and I think they work better. The problem with erythromycin, of course, is that if you don't take it with food, it's a gut bomb, and it really tears you up, I can't take it on an empty stomach myself, it's a little more expensive than tetracycline, it's a useful product, but I really don't like it as well as the other cyclines.

Doxycycline

And my favorite is Doxycycline. Even in the Sun Belt, this is my favorite, and if I can use it in Tucson, Arizona, you can use it anywhere. I have had a couple of residents from Toronto who came down and trained with me for a month, and they said, We don't use any Doxycycline because of the phototoxicity, and I said, You're in Toronto, and you don't use it because of phototoxicity? I've probably treated 20,000 patients with it in Tucson! So, you can use it, but you have to be cautious. The dose is 100 mg b.i.d. Now, let me tell you that doxy- and minocycline can be taken with food. And when you write the prescription, please remember this: you must write it that way; to take it with food; it softens the GI side effects. Because if you don't, the pharmacist will usually tell them to take it on an empty stomach. And if so, it can become a gut bomb, too. And you have to take it with enough water to wash it down, or you can even take it with milk, so it doesn't get hung up in the esophagus, or you will get definite heartburn; you must take it when you're still vertical for at least a half hour, because if it dissolves in the stomach, and you lie down right away, and it runs uphill, you can get heartburn from that, too. So there are some directions for taking these. Take it with food, otherwise the pharmacist will tell them to take it on an empty stomach. They cannot countermand what you write, if you write "with food." We're working around the pharmacy people sometimes here.

Phototoxicity is relatively common, but manageable. How do you manage it? Well, you avoid the sun. If you're going to have a big sun exposure, use at least a 30 rated sun screen, and if you're going to go snow skiing, water skiing, to Disney World for the day, something like that, you stop the doxy for at least 24 hours before you get that first sun hit. This is a very long-acting medication, as is minocycline, so you can't just stop the morning dose just before you pop into the sun - you have to stop it the day before. And I have 90% of my patients, even in Tucson, can use this, not 100% of them. Take it with food, and take it while you're still vertical.

Minocycline

Minocycline is the same dose, the same directions in terms of how you take it. However, it has many more side effects than doxycycline, and I don't like it as well for that reason. It is a favorite of dermatologists who uniformly believe that it's better than doxy, but to be honest with you, head to head studies among all the cyclines are virtually lacking. I think tetracycline taken as directed is actually quite good. Doxycycline taken as directed is quite good, this is quite good for acne for sure, but it does give an incidence of true vertigo, 8th nerve side effects are not common, I would put it at 5%, but I always start my patients on 1 pill a day for the first two weeks to make sure they don't get that vertigo, and then I move to 2 pills, and it seems to work out well that way. It gives you a tattoo-like pigmentation, it looks like bruises that don't go away, sometimes on the face, more often on the legs, especially of young women, and it looks like bruises that don't go away, and it's a tattoo-like pigmentation, and you want to stop the medication fairly early, because it can be permanent if it's there for months and months, or years and years. It can also cause darkening of the mucous membranes, and occasionally even blackening of the teeth which can last as long as five years! So the pigmentation thing is something I don't like to see, and I do warn about. It causes other things which are very rare, and I don't warn about, but I have seen toxic hepatitis, and I have had two cases of lupus-like disorder with this. So I am beginning to dislike minocycline more and more, and I don't use it nearly as much as the other medications. I do not tell patients that I can give them lupus or rot their liver with a zit treatment, I mean, you really can't do that. But I do tell patients that if they feel sick, if they feel unwell in any way, let me know, because there are a few oddball side effects of minocycline which I don't go through in detail. The rest of it is just like taking the doxycycline, except this one does not cause phototoxicity, and you can use it in your patients that are out in the sun, archeologists, life guards, and things like that.

Oral Contraceptive Therapy

Oral contraceptive therapy: I think everybody in the room probably prescribes more oral contraceptives than I do, so I'm just going to skim through this. I have been using oral contraceptives for acne for 25 years, since the day I started my dermatology residency. Just a few years ago, Ortho-Tri-cyclen was smart enough to push through an FDA approval indication for the drug, it was a very smart thing for them to do, so suddenly the whole world knew what I had known for the last 25 years, that it's very good treatment for acne, and now there is another medication, I can't remember, another one that has that indication, too, but it doesn't make any difference which one you use. All of the combination products work very nicely that are listed here. Now, those with more androgenic than progestational agents, Ovral, Lo-Ovral are some of those, and some of the ones that have only progestational agents that are a little bit androgenic, they probably actually work too, but you can a little flare before they get better, and I don't usually use those for that reason, but in fact, there are good studies on this, but I think these agents don't work as well, and you may get a little flare before they begin to work. Norplant, which fortunately isn't used much anymore, will significantly worsen acne, and Depo-Provera often worsens acne. So which contraceptive you choose makes a difference, but basically all the combination products work, and I think that the new patches that are out, that basically mimic the combination products also work. So I think contraceptives are major treatment for our female patients, and I think we should encourage those.

Accutane

Now, I'm going to go through Accutane a little bit, but I won't cover everything about it. There is an extensive handout on caveats for Accutane for primary care physicians, so I'm just going to open the door for you a little bit. This is the most effective agent in severe nodular cystic acne which has failed conventional treatment, and you should fail conventional treatment before you use this. It's used after those agents fail, it is severely keratogenic. So I think all females must be on contraceptives before this. Everyone has minor side effects, mood disturbance is very controversial, I personally believe it happens at a 2-5% incidence, I've seen both worsening of depression and de novo depression, I've seen anger outbursts, I believe we need to monitor moods while we're on this, so it's a very controversial area.

The side effect profile, extensive side effects, Review-of-Systems must be reviewed with each monthly visit. The new guidelines are very appropriate guidelines from Roche, severely limit the prescribing of this. You have to have these little yellow stickers with each refill, you cannot do phone refills, etc., and frankly I think all of this is good, because I think this needs to be severely limited to prevent the teratogenic side effects.

There is an attached handout on caveats for primary care physicians who prescribe this, and I'm just going to open the door on that by saying this is a very complicated medication, it was originally researched back in the 70's as a chemotherapeutic drug, not as a drug [for acne]. They're working at the NIH, and it is still used in multiple tumors. It is used to treat epithelial tumors, such as disseminated squamous cell carcinomas that have metastasized, it can be an effective treatment in cutaneous T-cell lymphomas, and adjuvants and numerous other tumor protocols that are used right now. This is a serious drug. It has the most numerous nuisance and serious side effects, more than any drug I use. I personally believe that Cyclosporin, Izathioprine and Methotrexate are easier to use than Accutane. But because it's zit medicine, people think they'll just look in the PDR and prescribe it. You can do that, but the learning curve is very long with this drug, and I'll just mention a few more things. It is the most potent teratogen ever available as a prescription drug.

Accutane embryopathy is comparable to, or worse than, thalidomide or congenital rubella, if you want comparisons. That means it's very bad. And a single capsule in the first trimester has produced the full-blown Accutane embryopathy sequence. So no amount of this is safe in the first trimester.

Both dermatologists and primary care physicians have had problems with its usage. Dermatologists sometimes tend to be cavalier about contraception, and have used it too frequently in nonscarring acne because of patient pressure, and I don't think that's the right way to use this drug. I think the primary care physicians receive relatively little training in the use of this, and they're also trained in other approaches to disfiguring acne, because you don't always need to use Accutane. But I'll have to say there are no secrets in my trade or Larry's trade, you can learn how to use this, but I would encourage you, if you're going to use it, go through the complete handout that I have on caveats for primary care physicians, and learn all of the side effects of Accutane. So, I think it needs to be reserved for the disfiguring scarring acne, and it needs to include failure on systemic antibiotics and oral contraceptives before you use it.

Click here for lecture handout: Accutane Caveats

Corticosteroids

I'm going to go back to the regular handout, and end up on three other therapies. Corticosteroids, prednisone, if you're in the midst of terrible scarring acne, or you're waiting for something else to happen, the patient's scarring down their face, can help to prevent scarring. If you put, or if you inject intralesionally (corticosteroids into the lesions), it can prevent scarring. Low dose dexamethasone is a controversial treatment which is probably best used for recalcitrant acne with a big stress component, it works better in women than it does in men, and it decreases adrenal androgens, use a tickle dose at nighttime, like .25 mg, a little controversial. I've had some experience with it, it is much less used, it was first described in about 1981, and Accutane came on the market right after that, so almost nobody uses this anymore, except me.

Spironolactone

Spironolactone is one of my secret weapons for women with acne. I won't go through every detail of this, because I'm just about to run out of time here, but it works at the oil gland level by blocking androgen activity, it's at the receptor level. It, of course, is primarily a blood pressure and diuretic, it's a weak blood pressure and diuretic pill, but not of great utility anymore. It does not have major effects that the kids and women that you give this to, they don't have to pee in the middle of the night frequently, they don't have hypotension, and so on, and you really don't have to worry about hyperkalemia in this, unless you're using it with other diuretics at the same time, which you're not doing when you're treating acne, so it's pretty simple to use. And the side effects are hormonal, midcycle menstrual spotting, occasionally amenorrhea, it can cause nausea, it can cause postural hypotension in people who start out with extremely low blood pressures to begin with, like some of those thin, asthenic women that are running blood pressures of 80/40, if you lower their blood pressure a little bit, they get posturally hypotensive. There is a pregnancy contraindication because it has a theoretical potential to feminize the male fetus, but I don't think that's ever been reported, but I often use this one in combination with oral contraceptives in women who have difficult acne to treat. I think it's a terrific treatment, I've treated over 500 women and adolescents with this, and I think it's a terrific treatment, it's underutilized by many dermatologists.

Summary