Anti-Inflammatory Therapy and Handling Infections

Excerpted from a presentation by Amy Paller, MD, at the 2010 National Eczema Association Patient Conference. Dr. Paller is the Walter J. Hamlin Professor and Chair of Dermatology and Professor of Pediatrics at Northwestern University’s Feinberg School of Medicine. Dr. Paller is also the Chair of the NEA Scientific Advisory Committee.

How do we manage atopic dermatitis or eczema? First, we need to do things that are going to help the skin to maintain its integrity. Avoiding things that disrupt that skin barrier or seem to trigger inflammation is important. This is an inflammatory skin disorder and we do use anti-inflammatory medications to try to suppress the inflammation. We use agents that fight microbes like bacteria in order to try to suppress infection.

For the past few decades, topical steroids have been the way that we treat eczema. These are not the steroids that are used by athletes to build up their muscles. These are steroids that are anti-inflammatory. The reason we use them topically (applying them to the skin) is so that we don’t have to take them orally and risk side effects. Within the group of topical steroids there are seven different subsets based on how potent they are. When we talk about hydrocortisone, whether it’s the 1 percent over-the-counter hydrocortisone or the 2.5 percent prescription one that is not that much stronger, this is low strength. This is class 7. On the other hand, we’ve got super-potent steroids like clobetasol or augmented betamethasone dipropionate, and these are all class 1. We need to be very careful using these. Stronger is more effective, so sometimes we use a stronger medication for a few days to jumpstart something, but we never use it on a chronic basis.

A common myth is that the percentage associated with a topical steroid means something. It only means something in terms of that exact steroid. If you have a 1 percent hydrocortisone, it’s not as strong as a 2.5 percent hydrocortisone. But if you have a clobetasol that is .05 percent then that outclasses a hydrocortisone of any strength in terms of its potency.

Topical steroids come in a wide variety of vehicles. We see them for eczema as ointments, creams, lotions, hydrogels, emollient foams, and oils. Sometimes we use different types of preparations for different areas, but also for different potencies. An ointment may be a little more potent than a cream, but it depends on the ingredients in that formulation.

The choice of topical steroid is based on a wide variety of factors. We’re not going to choose clobetasol when a baby comes in. On the other hand, if we’ve got an adult with really difficult hand eczema, we’re not going to use hydrocortisone; we’re going to have to go to something significantly stronger because body site also makes a difference. The face and groin areas are much more sensitive to the side effects as well as to the potency of the topicals. And we’re not going to use something strong on a mild to moderately affected individual as opposed to a severely affected individual.
It’s important to recognize that steroids suppress inflammation, but they’re not a cure. We don’t have a cure for eczema. We have ways to deal with it. When we’re using our anti-inflammatories, we are suppressing it.

What are some of the risks of steroid use? If used appropriately, there is low risk. I’ve been practicing for more than 30 years and I have seen only a handful of kids with clinically detectable evidence of problems. If you are using a more potent steroid, you must follow directions and use it carefully. There is no advantage in using a steroid more than twice daily. There’s no advantage to putting on a thicker layer. Just put on what’s needed to keep the area under control. We adjust what we’re using based on what’s going on in that particular area of skin. If you put the topical steroid just where the problem is, you can tackle it right there without the high risk that we can see when using an oral medication. Using too much, or too strong a steroid, can lead to an increased risk of internal absorption. Work carefully with your physician to make sure that you’ve got a whole armament of anti-inflammatories to use so you can adjust the potency to meet the need, including the use of different topical medications for different areas of the body.

n addition to topical steroids, we have calcineurin inhibitors. They have been a mainstay of our practice, and I think that they’ve been an important addition for the past 10 years. There are two of them. One is the pimecrolimus cream and the other is tacrolimus ointment. The tacrolimus ointment is available in two strengths. Calcineurin inhibitors are more targeted than topical steroids. They suppress the inflammation in eczema but they don’t have as many other effects so they don’t thin the skin. There’s a long list of potential side effects with internal absorption of steroids that we don’t tend to see with these. The only real side effect to date that has been shown to be significant in trials has been potential burning or stinging when applied.

Why don’t we use more of these and how are these best used? In my opinion, the strongest of these, tacrolimus .1 percent ointment, is about the strength of class 4 topical steroids. If you’ve got severe eczema and you’re markedly flared, you may be lucky and it may work. It may not be what you need to hit a severe flare. I use these more to try to keep things under control and avoid having to go back to the topical steroid.

The calcineurin inhibitors have been available now for 10 years, and I will disclose that I was involved in the initial trials and continue to be assessing their safety through the ongoing long-term 10 year trials. Topical pimecrolimus is approved for children 2 years of age and above in its single 1 percent cream formulation. Topical tacrolimus is approved for children two years of age and over at the 0.03 percent concentration and for adults at 0.1 percent concentration because of pivotal trials. However, the safety profile of the 0.03 and 0.1 percent concentrations in children over 2 years has not been found to be different, and I write more prescriptions for children of the .1 percent ointment as an off-label indication than I do the .03 percent because I find the 0.1 percent concentration to be more effective.

I think many of you have heard about this group of medications and have heard about something called a “black box warning.” Our Food and Drug Administration has a responsibility to protect the safety of Americans using medication, and they use black box warnings to alert people if something comes up. In the case of this group of medications, there was a growing concern not because of anything that had occurred yet, but because of a theoretical risk. When tacrolimus is given orally to profoundly suppress the immune system (as in transplant patients), recipients of this medication have an increased risk of tumors. One of these is called post-transplant lymphoproliferative disease. It’s like a lymphoma, and is related to the dosage of medication. Unlike lymphoma, it often improves or clears when the dosage of oral tacrolimus is reduced or when it is discontinued. We also know the transplant group as a whole when exposed to ultraviolet light has an increased risk of developing skin cancer. Thus, there is a theoretical risk of the development of these malignancies based on the experience when the medication is given orally in high doses to make people immunosuppressed. In contrast, there is not much if any absorption internally when individuals with eczema are treated on the skin with topical tacrolimus, so there is not any internal immunosuppression. To date, there has not been any evidence of a causative relationship between calcineurin inhibitors and malignancy, including in children.

What about when topicals aren’t working? One possibility that should be strongly considered is whether there is associated infection. Bacterial infection is particularly common with moderate and severe atopic dermatitis. The major culprit is a bacterium called Staphylococcus (Staph) aureus. Why is there Staph aureus on the skin? One reason is that the skin barrier is not normal in eczema. There’s a deficiency of some key components to the barrier. One deficiency that has received a lot of press lately is filaggrin. For some people, there is not enough filaggrin produced because of a gene problem. In others, the inflammation itself is enough to decrease the amount of filaggin in the skin, thus making the skin barrier less effective at preventing water loss and keeping out unwanted potential triggers of inflammation. Because the inflammation of eczema itself decreases the ability of the skin to produce filaggrin, we get into a cycle. The more inflammation, the worse the barrier, and this goes on and on unless we can somehow correct this.  Lipids are fats that are also important in our skin, particularly lipids called ceramides. Ceramides sit in the upper layers that are the barrier against allergic triggers, against bacteria, against all kinds of things that could otherwise get through, and they also help to protect against loss of water from inside the skin. Another reason for skin barrier abnormality is because of the active breakdown of the barrier by enzymes in our skin called proteases. The activity of these proteases goes up under certain circumstances, like when we use soap, which increases the local pH, the acid-base balance of skin. In addition, there is a natural decrease in eczema skin of proteins that fight off bacteria and virus infections. These are called anti-microbial proteins. It’s been clearly shown that the inflammation not only suppresses filaggrin production but also the production of our own antimicrobial proteins that fight off infection.

I want to talk to you about antiseptic baths because we’ve used these in our practice. I think if you’re not taking these baths, you’ve got to get with the program. This is now standard care in the United States for maintenance of skin with moderate to severe eczema, especially if there’s been any history of skin infection. We recommend these baths at a minimum two times a week and daily for most patients, and we stress that patients make sure to apply moisturizer right after the bath.

The use of dilute bleach baths (adding about 2 teaspoons of bleach per gallon of water, or ½ cup per full standard tub) is a maintenance practice that helps to maintain better control of the eczema in addition to decreasing the evidence of Staph aureus infection.
In summary, current therapies need to be directed to decreasing inflammation, improving the skin barrier, and decreasing bacterial colonization and infection. You’ve got to take all of these measures in order to have the best result.