Patients with psoriatic arthritis (PsA) experience high rates of pain and fatigue. Even when peripheral inflammation is suppressed, central sensitization can cause ongoing nociplastic pain that requires targeted treatments. Residual neuropathic and nociceptive pain may also occur due to structural damage. While biomarkers and current assessment tools remain limited, clinicians must rely on clinical experience to recognize pain etiology in their patients with PsA.

While the clinicians of patients with PsA are focused on suppressing underlying inflammation, patients with PsA are very focused on controlling their pain. Pain is an ever-present issue for these patients, and it erodes their daily quality of life when it is not treated properly. The second most important issue for patients with PsA is fatigue. It turns out that the fatigue associated with inflammatory immunologic conditions (eg, PsA, rheumatoid arthritis, and lupus) is caused by inflammation molecules affecting centers in the brain that signal “tiredness.” When patients are treated effectively, one of the first things that is lifted besides pain is this feeling of fatigue. Educating patients about the fact that pain and fatigue can be caused by the effects of inflammation, not only at the peripheral joint level but also in the central nervous system (CNS), is important, and it is a goal of treatment.

Historically, clinicians have primarily associated PsA-driven inflammation with nociceptive pain. This type of pain is like the pain you feel when putting your finger in a flame; your nerve endings immediately relay this signal to the CNS, which makes you jerk your finger away. However, there are other forms of pain, including nociplastic pain, which is an overreactivity of the CNS, and neuropathic pain, which is caused by injury or damage to the peripheral nerves. Individuals with PsA can have all 3 forms of pain, and it is important for clinicians to recognize this so that they can choose the best treatment for their patients.

In many studies, including some of our studies in the CorEvitas Psoriatic Arthritis Registry, we can see anywhere between 10% and 30% of patients with immune inflammatory diseases having this central pain phenomenon, known as nociplastic pain. So, even when we dampen down inflammation, the swelling goes away, and the laboratory markers of inflammation have normalized, a patient with PsA can still have ongoing pain and fatigue because of the phenomenon of central sensitization. We need to think about the possibility that nociplastic pain (ie, fibromyalgia) is present—not to shift from one biologic to another, but instead to intervene with treatments such as duloxetine, which can boost the effects of serotonin and norepinephrine in the CNS and is more specific for nociplastic pain.

In research, we do functional magnetic resonance imaging to tell us about pain and fatigue processing in the CNS, but this is not something that we can do in everyday clinical practice because we do not have good biomarkers or the testing capability. This is where the art of medicine comes into play: we need to have a certain amount of wisdom and understanding as we talk to our patients with PsA about the quality of their pain and fatigue. This way, we can ascertain whether we have controlled their inflammation adequately and whether there are other possible contributions to their pain experience.

There are questionnaires that we use in research settings, such as the Widespread Pain Index (WPI) and the Symptom Severity Scale (SSS), that form part of the fibromyalgia diagnostic criteria and give us a good sense of whether there is central sensitization–related pain occurring. This is something that we employ in our practice as part of longitudinal registry research. And now, as people realize that this is a confounding issue when interpreting clinical data, we are beginning to see some of these questionnaires enter into clinical trials. For example, in the UPSTAND study, which assessed upadacitinib for a related condition (axial spondyloarthritis), almost 49% of patients had high scores on the central sensitization questionnaire, even though fibromyalgia was an exclusion criterion in the trial. However, I would say that it is not quite ready for prime time in clinical practice.