It's been one year since NEA, in collaboration with four peer patient advocacy organizations, hosted the landmark patient-focused drug development (PFDD) meeting dedicated to eczema.
Published On: Dec 1, 2016
Last Updated On: Dec 1, 2016
All of our therapies target what we call “the cornerstones of eczema” — the itch, infection, inflammation, dryness, and inherent barrier defects that are involved with eczema. Because we unfortunately don’t have a cure that will reverse eczema right now, we focus our therapies on these cornerstones.
Similar to many skin diseases, the treatment for eczema is not a “one size fits all” situation. Eczema treatment evolves over time for each individual patient. What works for you at one point in time might not work in a different season or 10 years from now. This can affect whether you need more or less therapy. You have to work very closely with your team of caregivers to ensure your treatment is best tailored for any given situation.
It’s also important to practice a strong foundation of skin care outside of what’s prescribed. All of our medicines are helpful, but they’re even more helpful if you’re already working with a strong foundation and a strong skin care routine. That baseline skin care — which includes engaging in healthy bathing practices, and the use of gentle products, moisturizers, and emollients — can also help as you taper off some medicines, which is really important as we look at your overall care.
In regard to topical therapies, among our first-line medications are topical corticosteroids, because they provide excellent effects for inflammation and itch. They can also combat dryness, depending on the thickness of emollient used.
It’s important to remember that not all corticosteroids are created equal; they come in many different strengths and have different chemical structures which can impact how effective they are. The vehicles in which they’re prepared can also have a big impact on efficacy. So whether you’re using steroid in an oil, ointment, solution, lotion, or cream can have an impact on how effective it may be.
Topical steroids are divided into seven classes, which range in potency from Class 1 (very potent steroids) to Class 7 (very weak steroids). The same steroid can have different levels of potency, depending on the solution in which they’re prepared. For example, in ointment form, mometasone falls in a high-potency class, but when you use the very same steroid as a cream, it falls in the medium-potency class. Knowing the name of the steroid doesn’t necessarily offer you all the information about the treatment because potencies can vary depending on how they’re formulated.
It’s also important to keep in mind that the percentages of active ingredients don’t always tell the whole story in terms of how strong the steroid may be. For example, hydrocortisone 1% ointment or cream (which can be found over the counter and is very common) is very mild and is categorized in the weakest class. But one of the strongest topical steroids has a listed concentration of 0.05%, (which is a very tiny number compared to the 1% hydrocortisone ointment or cream, even though it’s much stronger).
In terms of their chemical structure, steroids are divided into classes, A, B, C, and D. Those within the same class have a similar chemical structure. If you’re looking to switch to a different steroidal medication, we often move to a different chemical class when picking which steroids to use.
The 2014 Consensus Statement on the Management of Eczema, published in sections in the Journal of the American Academy of Dermatology, gives us guidance regarding choice of topical steroids. We use very different steroids on infant skin than we do on adult skin, for example.
Areas of the body can also affect our choice of best steroid, such as whether we’re treating thick skin (on the scalp or the back) or thin skin (on the eyelid or genitals).
Certainly, the degree of dryness can impact whether we might want to use an ointment or a cream preparation as well.
Patient preference is another important consideration. I’ve had many patients who have told me, “I’ll do whatever you say but if you prescribe an ointment, I’m just not using it.” Because it doesn’t help to prescribe a medicine a patient won’t use, it’s important for doctors and patients to take preferences into account.
Finally, cost plays a part in steroid choice. Some insurance companies cover different steroids at different degrees, and some steroids are, unfortunately, a little harder to get than others. We take that into account when selecting the best steroid option for a patient.
Generally speaking, it’s recommended that steroids be applied twice a day. Fortunately, the skin can tell us when it’s absorbing too much medicine; this is when we start to see side effects in the patient. Side effects of topical steroids most commonly initially present on the skin with signs such as increased blood vessels or thinning of the skin.
We provide physical exams to monitor for skin side effects. If we see a lot of side effects on the skin, then we also begin to think about how systemic side effects may affect the body internally. This is especially important to watch for when using steroids on large surface areas of children’s skin, in patients who have a lot of skin breakdown, or when the steroid application is covered (occlusion) in order to increase potency.
As a general rule of thumb, we use the fingertip unit of measurement to decide how much of a steroid we need to apply. The fingertip unit refers to the amount of steroid in a small strip on that very last portion of your finger (from the last joint to the fingertip). That one fingertip unit will be enough medication to cover the skin on two adult hands. From there, we scale the amount up or down accordingly.
We also encourage proactive use of a topical steroid treatment on “hot spots,” or areas that commonly flare. If you’ve worked very hard to get your eczema under control, and things are nice and quiet, a lot of times we recommend intermittent use of the topical steroids as maintenance therapy because continuing the use of steroids on those hot spots can prevent relapses. This has been found to be more effective than just using emollients alone.
Another category of topical treatments consists of the calcineurin inhibitors, tacrolimus and pimecrolimus. They also work to reduce inflammation, improve itch, and can combat dryness—especially when used in an ointment formulation.
It’s important to talk about these options with your doctor before starting them because they have an FDA black box warning, which was added to the pack- age labeling in 2006 as a response to a strong increase in use of topical calcineurin inhibitors as an alternative to steroids, and there is data suggesting an increased risk of cancer (which is particularly important if these medications are used in their oral formulations for long periods of time at high doses, such as with immunosuppression conditions).
I like to have an up-front talk with my patients about this potential risk and explain to them that our use is topical, in limited focal areas, and that I find (along with the American Academy of Dermatology and many other providers) these topicals to be very safe for long-term use in a controlled manner for eczema. It’s important for patients to be informed of this labeling prior to picking up a prescription for the first time and noticing the FDA warning on the packaging.
In many situations, the use of a topical calcineurin inhibitor is preferred over that of a topical steroid. One instance is when the skin has become resistant to steroid use in sensitive areas, such as the eyelid or the lips.
A topical calcineurin inhibitor may also be the best choice when side effects from topical steroids begin to show in the folds of the skin, where you might have too much steroid absorption.
Topical calcineurin inhibitors can also be helpful in places that are already showing signs of steroid-induced changes such as atrophy. Similarly, if you’ve been on a topical steroid for a long time and are looking for a break from steroid use and would prefer to rotate another medication in, topical calcineurin inhibitors can be very helpful.
Topical antimicrobials and antiseptics are medicines that are applied topically in efforts to reduce bacteria, though the 2014 Consensus Statement on the Management of Eczema designates only specific scenarios where they are recommended for eczema, specifically, in patients who have moderate to severe eczema and signs of infection on top of their eczema (called secondary bacterial infection or superinfection). For these patients, dilute bleach baths and mupirocin used intranasally to reduce the colonization of bacteria on the skin are often recommended to reduce the severity of eczema.
Topical antihistamines also help many patients, but the 2014 Consensus Statement does not recommend their use for eczema specifically, mainly due to the risks of absorption and contact dermatitis that patients can develop from them. Many patients do bene t from them, however, so this is another one of those situations where individual patient preferences and conditions must be taken into account.
Other topical treatments available that have been used for eczema include tar, biologic devices, and others in development. Tar has been used for many years and studies have shown that tar is about as effective as 1% hydrocortisone. There are biologic devices, such as Epaderm and Atopiclair, which are prescription-only topicals designed to work on the skin barrier. There are also topicals in development such as the phosphodiesterase inhibitors, which may be used to treat eczema in the future.
Phototherapy is the controlled delivery of ultraviolet (UV) light for anti-inflammatory purposes. It’s effective for many patients, but safety is always a priority. With this in mind, when patients start phototherapy, their first treatments are sometimes as short as 15 seconds of exposure. Over time, the length of sessions in the phototherapy unit gradually increases.
Treatments are individually tailored depending on skin type, tendency to burn, the amount of pigmentation, and the response of the patient’s eczema. There are different types of wavelengths of light that can be delivered, including UVB, UVA1, or a combination of ultraviolet lights.
Often patients start out with three sessions a week, and typical phototherapy courses last three to five months. I tell my patients to expect to undergo 15 treatments (for a duration of at least five weeks) before considering whether it is helpful. This is not a quick fix, so I make sure that everyone knows that it’s a commitment, because I want my patients to give it a fair shot.
Sometimes patients are prescribed psoralen, which is a photo-activating medication that can be taken orally or applied topically before light exposure; it gives patients an extra boost of a response.
Finally, in some parts of the country the Goeckerman Therapy regimen is used. In this therapy, tar is applied to the skin lesions, which also makes patients more sensitive to the light from phototherapy.
Selection between these options depends on local availability. Cost is also an issue, as many insurance companies, unfortunately, are charging co-pays with every phototherapy visit.
Patient skin type, current medications, and whether patients have had skin cancer in the past are also factors in how light therapy impacts skin. For example, some patients exposed to phototherapy may have a more vigorous response if they are also taking certain antibiotics and/or hypertensive medications that are common in the general population. All of these factors must be taken into consideration.
According to the 2014 Consensus Statement, phototherapy is considered a second-line treatment. If the use of emollients, topical steroids, and topical calcineurin inhibitors fail, then phototherapy can be used as a maintenance therapy. Phototherapy should be performed under the supervision of a doctor who is experienced in managing the treatment. Additionally, phototherapy units are sold for home use, and can deliver the therapy safely as well.
Mother Nature’s phototherapy is also called “heliotherapy.” In my experience, patients who do well with phototherapy tend to tell me that their skin is best in the summer. This may be due to a combination of natural sunlight and summer activities, such as spending more time in the swimming pool (something that may deliver a bleach bath-like effect). I take patients’ input very seriously in considering whether phototherapy might be an appropriate option.
Antibiotics, antihistamines, and many anti-inflammatory medicines are used as oral medications for eczema. Antibiotics can be particularly helpful if there is clear evidence of active Staph infection, as an antibiotic may help alleviate oozing and painful skin. For those patients who improve with frequent administration of antibiotics (which signals they may have a high burden of bacteria that may be aggravating their eczema), I often suggest regular dilute bleach baths or other decontamination measures.
Antihistamines tend to work for eczema by helping to induce sleep and reduce loss of sleep. Antihistamines can also help patients who have eczema and allergies or eczema and hives concurrently. When looking at eczema alone, however, antihistamines haven’t really been shown to change the skin disease itself. In the absence of hives, non-sedating antihistamines are not recommended for the management of eczema.
Systemic anti-inflammatories are generally indicated for patients who do not respond to the optimal topical regimens and have tried many different iterations of topical steroids. For these patients, working closely with their doctor to tailor treatment for their needs is important.
I always start by talking about systemic corticosteroids or oral prednisone because so many patients tell me that they were on prednisone for either their skin, or asthma, or another reason, and found that their skin improved quickly.
Unfortunately, when patients stop taking the medicine, the skin flares like wild fire, often harder to control than prior to oral steroids, so that’s something to be aware of.
It’s thought that systemic corticosteroids are best avoided when it comes to long-term management for eczema patients, because the temporary bene t is outweighed by the short- and long-term risks. However, they can be used for a short period of time in order to help transition to another medication or phototherapy to get the disease under control. Systemic corticosteroids can be a quick fix, but unfortunately can pose problems if you’re not focused on how you’re going to taper off from these oral steroids.
In terms of other systemic treatment options, there is evidence-based data for a number of medicines. The 2014 Consensus Statement addresses four of them: cyclosporine, methotrexate, mycophenolate mofetil, and azathioprine.
I don’t like to use these medicines unless absolutely necessary, because they all have significant toxicities. They do have a place in care for when they’re really needed, but when we do use them, we like to use them at the lowest possible dose for the shortest amount of time in order to minimize the associated risks. Unfortunately, they’re not perfect and they’re not a cure. They are helpful in many situations and I think based upon the guidelines, we do want to make sure that we’re all aware of them.
Cyclosporine was originally isolated from a soil sample in Norway in 1969 and some people consider it natural because it’s from the soil. It was developed as an immunosuppressive medication used to prevent rejection of organs after transplantation.
In my experience, Cyclosporine works very quickly and we think of it as a rescue medication to be used for a short period of time to get skin under control.
When prescribing cyclosporine, I make sure that I’m screening the patient appropriately, monitoring the patient closely, and educating the patient of the many things to consider. I think about which medications it may interact with and whether the patient has an underlying cancer, since cyclosporine impacts the immune system.
It’s also important to monitor blood pressure in these patients and at least two baseline normal blood pressure measures are needed before a patient can start this medicine. Some side effects of cyclosporine include hypertension and elevating lipids, so we monitor patients very closely with monthly labs in order to minimize these potential side effects. We also try to keep this medication course very short: six months at the maximum.
Methotrexate was initially discovered as a compound similar to folic acid and has also been around for quite a long time. In the late 1940s, it was used for children with leukemia, and at high doses methotrexate is still used as a chemotherapy.
At low doses it’s pretty well tolerated for autoimmune diseases. Methotrexate is given once weekly, and can be given orally or by injection.
It does have serious medication interactions and affects fertility. It can also cause side effects in both the liver and the lungs, so we monitor patients regularly, especially as the dose is being adjusted. In all, this medication is one that we’re comfortable using when we need it because has been around for a very long time and is used for a number of different purposes.
Azathioprine is another serious medication that was initially developed as a cancer drug in the late 1950s. Because it interferes with the synthesis of DNA, azathioprine relies on the body to metabolize it.
We all have an enzyme in our bodies called thiopurine methyltransferase (TPMT), and for patients who have low levels of this enzyme naturally, azathioprine can build up in the bloodstream and cause serious unwanted effects. For these reasons, we always check for the levels of this enzyme before using azathioprine so we know whether the medicine is safe to take.
We’re also concerned about medication interactions and side effects, including sun sensitivity, trouble with fertility, and even more side effects when used as chemotherapy. It requires the monitoring of labs and is a serious immunosuppressant, which is one reason why I’m glad that there is another medication that targets the same pathway: mycophenolate mofetil.
Most people know mycophenolate mofetil by the brand name CellCept, a drug tolerated without difficulty by many patients. Though it targets the same DNA synthesis pathway as azathioprine with far fewer side effects, it still causes serious side effects, which require monitoring. The most common side effects include gastrointestinal issues, like nausea or irregular bowels.
For patients taking this drug, we monitor for bone marrow and liver toxicity as well, in order to make sure the medication is being tolerated safely. It is also harmful during pregnancy.
There are ongoing studies for a number of medicines.
We have patients at Boston Children’s Hospital with both immune deficiencies and eczema, who really benefit from treatment with intravenous immunoglobulin, also called IVIG. When these patients’ own immunoglobulins are not at sufficient levels, we find that when given infusions of IVIG, their eczema and skin seems to improve. Another drug, Interferon gamma, has been shown to be effective in many trials.
Unfortunately, it has side effects which sometimes limit its use. And, of course, I want to mention Dupilumab, which is the new medication I recently read about and discussed previously. [Ed. note: dupilimab was approved for use in March 2017 for adults with moderate to severe atopic dermatitis].
Currently, on clinicaltrials.gov there are many open studies for atopic dermatitis. Many supplements are being tested for benefit for eczema, along with some new moisturizers.
Though the pathways are different, we are starting to see whether biologics relevant to psoriasis might be helpful in eczema. There are many more drugs in development.
It’s helpful to remember that prescription medications work best when used in conjunction with a strong skin care foundation. It takes a lot of teamwork to address patients’ changing needs, so work together with your prescriber to make sure that the regimen is exactly right for you and that treatment adjustments are made during flares.
The skin can flare for so many different reasons — whether it be environmental or incidental illness — so you need to understand what to do to ramp up therapy when you need it and how to scale down when you don’t. Of course, we love scaling down, getting back to that baseline foundation whenever we can.
Hopefully with all of these efforts, you’ll be happy with some improvements in disease, and we can all keep our fingers crossed and hope for an actual cure in the future.