Q: Is RA very much like other chronic pain syndromes in regard to fatigue and depression, or is there also something unique there?

The only difference between other chronic diseases and this one is the significant pain aspect, which can contribute significantly to psychiatric overlay. One of the foremost challenges clinically is the concomitant fibromyalgia or chronic muscular pain—which has a good deal of psychological overlay. Aside from the consideration of fibromyalgia and psychologically associated illnesses, I don’t think that it’s different from other chronic diseases that involve pain.

Another way to think about this is the way that I was taught a number of decades ago by my teachers, who said, “This is not rheumatoid arthritis; this is rheumatoid disease.” We all know that its major phenotype is joint inflammation. However, this is a systemic illness. We see vasculitis, pericarditis, pleuritis, anemia, etc, that’s related to this disease. We bear in mind that, although the joints are clinically most relevant, there are systemic features in addition to the joints. There are also important comorbidities, such as the increased cardiovascular risk, the increased risk of malignancy, and the increased risks of infection—along with what is being called out in this particular question, which relates to the issues of pain, fatigue, and depression. We have come to learn that one of the most important—if not the most important—cytokines in driving many of these extra-articular features of RA is IL-6.

Just to add, in going back to the question of how RA may be different from other chronic, painful diseases—I think that it’s a very interesting question. The epidemiology of intercurrent mood disorders in RA is actually a matter of controversy (ie, whether these disorders are overrepresented or underrepresented). I just saw some data this morning by Clifton O. Bingham 3rd, MD, Director of the Johns Hopkins Arthritis Center. These data relate to the Patient-Reported Outcomes Measurement Information System (PROMIS) scores from their rather large group of patients with RA. And, actually, this group’s mental health profile was almost identical to the population norm. Yet, as Dr Furst pointed out, we do have perhaps one-fourth of patients with RA who have varying levels of central pain sensitization, and these patients clearly have overrepresented mood disorders. And I would agree with what Dr Epstein said, in that I believe that this phenomenon is not incidental. Inflammation and numerous cytokines, including IL-6, may be complicit in disrupting sleep, increasing fatigue, etc. In fact, the role of inflammatory cytokines in the pathogenesis of mood disorders is a whole new, burgeoning area of interest, and there is interest in potentially targeting inflammatory cytokines in the treatment of mood disorders—depression, in particular. It’s a complex area and it’s becoming more interesting as we move along.

I always think of my patients with RA as some of the most courageous patients I know. Most of them are straight shooters, and most of them are stoic. Of course, there is somewhat of a normative distribution within the population, and you get that variation. However, in contrast to other patients with central pain syndromes or somatization disorders and the like, I find the patients with RA who suffer from these phenomena to be somewhat distinct.

I agree with what has been said. I would add that another unmet need in this area is that of measurement (ie, the use of quantitative RA measurement tools). Unfortunately, the uptake of these assessment tools in the real world is not as good as we would like. Even with the Routine Assessment of Patient Index Data 3 (RAPID3), which should be an absolute “no-brainer” for the physician, the data suggest that uptake has only been around 30%. And so, we’ve got a ways to go.