Addressing Itch

Atopic dermatitis (AD) has many unpleasant symptoms, but one of its hallmarks is itch. AD itch may plague doctors as much as their patients because it is so complex, and there is still so much not yet understood about its role in the disease. To get a better grasp on that role, The Dermatologist spoke with Alan Fleischer, MD, professor and residency program director of the department of dermatology at the University of Cincinnati College of Medicine in Ohio. Dr Fleischer is the author of The Clinical Management of Itching and treasurer for the International Forum for the Study of Itch. 

Q. How big of a problem is itch for most patients with AD? 

A. It is the primary, and most distressing, complaint by far. People with AD may also experience pain or burning, but the severity of itching is really notable. And the intensity is largely determined by the severity of disease. With relatively trivial disease, itch is usually minor, whereas with more severe disease, itch can be disabling.

Q. How does one assess itch severity? 

A. That is an evolving area of research. We have relatively good measures of AD severity, such as the Investigator Global Assessment, for clear, almost clear, mild, moderate, and severe disease, as well as Eczema Area and Severity Index scores. By contrast, itch is a subjective symptom and only the patient can tell you how bad their itch is. One way of assessing it is to ask the patient to assign their worst symptoms from the past 24 hours a number on a scale from 0, which is no itch, to 10, the most severe. If the patient appears to have moderate disease, yet they are reporting a 10, there is a disconnect. Or, the reverse might occur, where someone has really severe disease, and yet they report very little itching. In general, though, the two align.

Q. Aside from disease severity, are there other factors that can exacerbate itch?

A. When people are experiencing episodes of stress in their life, the stressors can make the disease worse, but they can also make the perception of the disease worse. It is a lot like chronic pain in that there is a biopsychosocial model for itch. It is more than just the disease state. It is really critical to understand that it is not just all disease severity related, but there are factors related to the entire person that mediate the sensation of itch. The biopsychosocial determinants include personality characteristics, external stressors, cognitive, behavioral, and social factors.¹  

Q. What determines whether itch is localized or generalized? 

A. There are many different genes that mediate the atopic state. Two people who both have AD will have different genetic makeups that affect how the disease presents. In time, we will likely have many different forms of AD that are recognized and categorized.

On top of that, there are environmental exposures that also seem to make it worse. Exposure to bacteria and viruses, to allergens, to irritants, and to a variety of other factors, including climatologic factors, also can exacerbate and/or relieve disease. It is actually very complicated.

Q. What do we know about triggers for itch? 

A. Triggers for itch in AD are clearly specific to the individual who is experiencing it. Some people, upon exposure to irritants or allergens, almost always see their itch worsen. Certain individuals typically experience more severe itch in the summer, for instance, while for other people, spring is worse. Both of them are telling the truth, even if they’re not telling the same story. It is not really the same condition in every individual. It is a variety of different conditions, and individualized management needs to be performed for that reason.

Q. What are some of the ways to treat itch? 

A. Strategies that can help include moisturizing the skin and avoiding irritants. Well-moisturized skin is much less irritable than dry skin. Also, people who have the atopic state are predisposed to be much more reactive to things in their environment; for instance, they are much more likely to develop allergic contact dermatitis due to common allergens in personal care products. There are lists of irritants and potential allergens, such as fragrances and preservatives, and some patients can, with the help of their clinician, identify those that seem to make their condition worse. Avoiding irritants, wearing soft clothing, and limiting exposure to extremes of temperature may all have some beneficial effect. In some individuals, however, there seem to be no precipitating factors. They just flare no matter what. 

Q. What is known about the physiological mechanism behind AD itch? Is it the same as other kinds of itch? 

A. Itch has many causes. Recently, I saw a patient who had a form of neuropathic itch­—itch due to nerve dysfunction—that should have been recognized likely 10 years earlier. There are a wide variety of other neuropathic diseases that cause itch. 

In most people, it is likely that AD itch is the result of skin inflammation, which is complex and has multiple mediators. It will never be as simple as, for instance, it is in urticaria. Many people with urticaria can be well managed just with an antihistamine, systemically. Antihistamines have never been shown to have any benefit in the setting of AD because it is not a histamine-mediated disease. As we go forward, relief will center upon relief of inflammation.

Q. How effective are the current treatments? 

A. People with limited disease on a small amount of body surface area, and those with short-term disease, can be well controlled with drugs like topical corticosteroids, which can be used safely for a few weeks. If their disease improves and they are able to stop topical treatment, there is little risk.

For patients who also have relatively limited body surface area, but who need more intensive treatment for longer periods, much safer long-term treatments are available topically, such as crisaborole (Eucrisa), tacrolimus, and pimecrolimus (Elidel). 

If a person has 30% or 80% body surface area involvement with severe disease and it has been going on a long time, the likelihood of controlling them with topical treatment is minimal. As a result, there are a variety of other approaches worth considering. Specifically, phototherapy can be helpful in some individuals and can decrease the inflammatory response. There are some old and poorly studied drugs that decrease inflammation, but their efficacy and safety is not well known. We now also have a systemic treatment option of dupilumab (Dupixent), which is the first of the available biologic treatments and has an indication for moderate to severe AD.

Over the next 5 years, we should get a dizzying array of new systemic agents with many different mechanisms of action. I’m looking forward to a day, 5 years from now, when we will have a large number of treatments to manage the inflammation of AD and we should be able to bring their itching under control fairly quickly.

Q. What about when these symptoms occur concurrently with pain or other symptoms? Do they have to be treated differently?

A. To the best of my knowledge, we do not necessarily treat those symptoms differently. One person’s itch can be another person’s searing itch, can be another person’s tickle, or another person’s burning itch. There can be different kinds of sensations that people have in the skin, and these sensations can be variable. As far as we know, though, if you calm down the inflammation, all of the skin symptoms go away.

Q. Does AD tend to improve over time?

A. Often there is change in the disease over time, but there is no evidence that the AD resolves. We have few cures for any dermatologic disease beyond skin cancer. But the typical AD we see in childhood often morphs into a different look in adulthood and a different clinical presentation. In some people, their disease is active for a series of several years and then becomes mostly quiet and they need much less care. Other people need treatment month after month, year after year.

Q. How would you like to see treatment of itch change?  

A. I would like to see dermatologists prescribe far fewer drugs that have no evidence of efficacy, such as antihistamines, which can be problematic in terms of their side-effect profile, and become far more adept at prescribing appropriate quantities and limited durations of topical corticosteroids. Corticosteroid-sparing topical agents and good skin hygiene—that is, bathing behavior and moisturization—can help quite a bit. 

Doctors also should not be bashful about taking the leap into systemic treatments, whether those be small molecule treatments or drugs like dupilumab, which now are well characterized in terms of their efficacy and safety profile and are often well tolerated. We are living in an era in which we will get increasing numbers of new treatments for AD within the next few years. We should have IL-13 drugs approved, such as lebrikizumab, among others. We will have hopefully an IL-31 drug approved. IL-31 seems intimately related to itching. We will have small molecule treatments approved, including Janus kinase inhibitors. 

We are about to enter revolutionary times when it comes to the long-term management of these patients. It is great to be living in an era of new and exciting treatments. 

Reference

1. Verhoeven EWM, de Klerk S, Kraaimaat FW, van de Kerkhof PCM, de Jong EMGJ, Evers AWM. Biopsychosocial mechanisms of chronic itch in patients with skin diseases: a review. Acta Derm Venereol. 2008;88(3):211–218. doi:10.2340/00015555-0452