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Evaluating AD-Related Pain in Clinical Practice

Jonathan Silverberg, MD, spoke with The Dermatologist regarding recent research into pain as a symptom of atopic dermatitis (AD) and how dermatologists can evaluate AD-related pain within clinical practice.

Dr Silverberg is an associate professor of dermatology and director of the patch testing clinic at the George Washington University School of Medicine and Health Sciences in Washington, DC.

What do we know about the type and characteristics of skin pain in AD?
There is not just one “type” of pain in AD but rather a mixture of different pains. Some pain is secondary to open sores or cuts in the skin, or a traumatic mechanical pain; other pain can be neuropathic. There also seems to be a rare subset of pain being exclusively driven by insensitivity or intolerance to personal care products and topical medications in approximately 10% of patients.1

There is a subset of pain that patients will endorse that occurs even in the absence of scratching. This type seems to be akin to neuropathic pain, or at least in that spectrum. In one study,2 we surveyed patients regarding their AD-related pain symptoms and compared the responses to the patient’s physical exam. Upon analysis, we found that approximately 58% of patients who endorsed pain actually had no visible scratching excoriations whatsoever.

However, when patients were asked to attribute their pain—ie, was it something that was more related to scratching, to the itch itself, or both—72% of patients reported that their pain was related to both. In fact, only a minority (11.2%) said their pain was purely related to scratching, which I think is quite provocative because most of us would think that the pain is all related to scratching. Patients who reported their pain as more related to their itch were likely to be experiencing more of a neuropathic pain. These patients used descriptors that are very similar to what we would expect with neuropathic pain: pinprick‑like, shooting, stabbing. Pain related to scratching and/or soreness tends to be described as dull or throbbing.

We were classically taught that pain suppresses itch, even though these symptoms run along certain similar nerve fibers. As it turns out, in AD, there is a subset where that is not really true, and itch and pain overlap quite a bit.

With these characteristics in mind, how can pain affect how we treat patients with AD?
We know about the importance of itch in AD. If pain only comes because the patient scratches their itch, then maybe the pain is a little less significant or less of a therapeutic target conceptually. This is not to say that pain is less burdensome, but research into new therapeutics would focus on addressing the pain indirectly via treating the itch. Given that a subset of patients with AD experience pain in the absence of itch or their pain even behaves differently than their itch, we cannot just assume it will get better simply because the itch gets better.

Some studies are now looking at the longitudinal course of pain. We found that, in a specific subset of AD patients, pain behaves very differently than itch over time. Pain is its own symptom. Yes, it is related to itch in many, but the course of pain is more similar to sleep disturbances or mental health comorbidities, such as anxiety or depression. Those are highly correlated with itch, but they present independently as well. I have seen patients who are super itchy who do not get those symptoms as well as patients who report pain, sleep and mental health disturbances but have a mild case of AD.

We need even more confirmatory studies to show that pain is a real issue in AD. To the patient, pain as a symptom of AD is a no brainer. I am not sure why exactly it seems so new to the clinician and why we have not described it. There are still many in the field who question this independent association, yet when you talk to patients, it is very clear that pain is a major problem.

In one of the follow-up studies from the Atopic Dermatitis in America Study,3 we assessed which symptoms were particularly burdensome to patients with AD. When we asked patients to rank their symptoms, itch was obviously the most common symptom, but in the moderate to severe cohort, pain was not uncommonly their most or second most-bothersome symptom.

There has been a steady increase in interest in research looking at pain, to the point that it is now being assessed in clinical trials routinely. Hopefully, we will have some meaningful data on how newer therapeutics potentially affect AD-related pain. However, we do not know how our older therapeutics impact pain, so there is an opportunity to revisit these options. A number of studies are trying to understand what is going on at a molecular level to answer the questions where is this pain coming from? and what are ideal treatment approaches to address pain?

I recommend that dermatologists stay tuned to this research. It is an area that is definitely growing in research, and with that, the goal is to reduce the lack of awareness in the medical community. Even from an advocacy standpoint, dermatologists should think to ask about pain, because it does matter to patients.

Given that pain is subjective to the patient’s experience, are there any options for qualitatively measuring AD-related pain to help guide treatment options?
Some qualitative research has been done regarding an assessment tool for skin pain in AD, and a numeric rating scale (NRS) modified for pain has been developed.4 From this research, it is clear that the qualitative experience varies for patients. What one patient calls a stabbing pain, another may call it soreness or even a burning sensation. These variances can matter, because it can frame how talk about skin pain with the patient and ask them about their symptoms. If we do not ask the right questions using the appropriate descriptors, then the patient is going to interpret our questions literally and we are not going to get the correct information.

As clinicians, we often come in with the assumption that AD is all about the itch and we do not focus enough on the extended symptom complex. It takes just a few seconds to ask the patient “On a scale of 0 to 10, how intense is your pain?” If they say it is zero, then it is zero, but if they say it is a seven, then that is probably a reason to step up therapy.

We have to make sure we understand that qualitative experience, and the best way to do that is to ask the right questions and appreciate just how bothersome pain can be to the patient.

How would you suggest incorporating AD-related pain monitoring into clinical practice?
From the world of pain research outside of AD, even after decades of research, we still do not have a biomarker. What pain comes down to is the patient-reported outcome and simply asking to obtain that information. The best practice is to use a NRS, either as a scale of zero to 10 or a verbal rating scale with choices along the lines of none, mild, moderate, or severe. A visual analog scale may be an option as well. Dermatologists can and should ask patients “in the past week or so, how bad was your worst skin pain?” That simple approach can be incorporated into clinical practice immediately.

We are starting to see the evolution and the arrival of some simple tools that can be used easily in any practice setting. For example, my research group has a manuscript recently published regarding the validation of a separate skin pain NRS for use in clinical trials or practice.5 Dermatologists just have to incorporate these tools. A single-item question should not slow down anyone's clinical practice, and it is not going to burden the patient or investigate more than a clinical trial.

We are at that point where we recognize that AD-related pain is burdensome and we have some valid tools to assess it. We just have to make sure there is a commitment to understanding this AD symptom more and figuring out what is the best way of addressing pain in these patients.

1. Silverberg JI, Gelfand JM, Margolis DJ, et al. Pain is a common and burdensome symptom of atopic dermatitis in United States adults. J Allergy Clin Immunol. 2019;7(8):2699-2706.E7. doi:10.1016/j.jaip.2019.05.055

2. Vakharia PP, Chopra R, Sacotte R, et al. Burden of skin pain in atopic dermatitis. Ann Allergy Asthma Immunol. 2017;119(6):548-552.e3. doi:10.1016/j.anai.2017.09.076

3. Silverberg JI, Gelfand JM, Margolis DJ, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018;121(3):340-347. doi:10.1016/j.anai.2018.07.006

4. Newton L, DeLozier AM, Griffiths PC, et al. Exploring content and psychometric validity of newly developed assessment tools for itch and skin pain in atopic dermatitis. J Patient Rep Outcomes. 2019;3(1):42. doi:10.1186/s41687-019-0128-z

5. Silverberg JI. Validaty and reliability of a novel number rating scale to measure skin-pain in adults with atopic dermatitis. Arch Dermatol Res. Published online February 6, 2021. doi:10.1007/s00403-021-02185-3


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