Skin pain in atopic dermatitis (AD) is not a newly identified characteristic, but the body of research on the topic is not yet robust. This is partly as pain was largely thought to result from itch, a prevalent symptom of AD. However, research like that of Johnathan Silverberg, MD, PhD, MPH at George Washington University School of Medicine and Health Sciences, and his colleagues, underscores that pain is quite common in AD. In fact, more than half of participants in Dr Silverberg’s study with the disorder experienced pain, although the underlying mechanisms varied.
We spoke with Dr Silverberg about his publication, “Pain Is a Common and Burdensome Symptom of Atopic Dermatitis in United States Adults.”
Your study found that about half (48%) of participants only had pain after scratching—which was associated with mild AD—and 42% of participants had intermittent pain, and this was associated with severe AD. In severe cases, does the inflammation itself cause pain?
Dr Silverberg: In some cases, it does. Pain is a bit of a heterogeneous symptom, and there are broadly about 4 different causes for pain in atopic dermatitis—1 is secondary to scratching; 1 is secondary to inflammation itself; 1 can be irritation or tolerability concerns related to topical medication; and the other can be related to fissures or cracks in the skin, particularly in certain body parts like the hands and feet. Patients with more severe AD have a higher probability of having pain without scratching or experiencing the other symptoms, and the pain is what seems to be the reason for the inflammation itself.
In AD, does scratching skin due to itch cause it to become more inflamed?
Dr Silverberg: Scratching will cause immediate pain; in fact, partially how it suppresses itch is by inducing a pain response. But then there’s a separate issue, which is the idea of the itch-scratch cycle—that by scratching the itch, patients may alleviate it transiently, but that causes further damage to the barrier, which will ultimately lead to more inflammation. This leads to the itch-scratch cycle, which can worsen the underlying disease.
What further research can be done on the nervous system as a mechanism for pain in AD?
Dr Silverberg: Much of the research recently has addressed the immune-mediated aspects of atopic dermatitis, and we’ve seen a lot of research on the barrier aspects. We’ve seen much less research in general on the neuroimmune synapse, and how the immune system triggers the nerves to cause itch, pain and discomfort. There are studies in animal research that have focused on what happens to the nerves in terms of increased nerve sprouting, but there’s a greater need to understand what it is about the immune system that triggers the sensations of itch and pain, what receptors are activated, what immune mechanisms are driving that. With that, we will eventually be able to identify treatment targets to address the itch and the pain.
In AD, why is pain on the hands and feet, compared with in other areas of the body, often described as excruciating?
Dr Silverberg: We know the hands and feet in particular have the highest nerve density on the body other than, perhaps, the genitalia, and it is there to protect us from injury and to give us maximal tactile sensation—so when we get injuries to our hands and feet, it can really have a profound burden in terms of pain. Movement in general, and stretching open wounds, hurts, and because we use our hands and feet more than other parts of the body, the wear and tear will aggravate open wounds. However, there’s a lot we don’t know about why some patients get more hand eczema than others, so there are opportunities to understand more about the underlying causes of eczema in those regions.
Do management strategies differ for various severity levels in AD?
Dr Silverberg: Our guidelines recommend the “step-up” approach to therapy, in which patients would be started on a more conservative path to begin with, and if they fail that, they would be stepped up to a more advanced therapy. In general, the more severe the patient is, the more likely they are to require being stepped up. So certainly, we are using things like systemic immunosuppressants or biologic agents or prolotherapy more so in patients with moderate to severe disease compared with mild disease. As it pertains to specific targeting of itch or pain, we don’t see any severity-based recommendations; it’s more treating the symptoms as needed.
Is there anything that you would like to highlight regarding pain in AD?
Dr Silverberg: I’ve spoken to clinicians who are naysayers about pain, but when you look at population levels, such as in our study, 60% of adults in the US with AD reported pain. This shows that it’s not just a biased cohort from our original clinical experience, and it’s not an isolated thing: this is a really common issue, and it’s something clinicians need to recognize. Multiple studies have now confirmed that pain is an issue in this disease, and it’s something that we need to pay attention to.
Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, Chiesa Fuxench ZC, Simpson EL, Ong PY. Pain Is a Common and Burdensome Symptom of Atopic Dermatitis in United States Adults. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2699-2706.e7. doi:10.1016/j.jaip.2019.05.055.