FM often coexists with RA. The prevalence of FM in the general population is roughly 3% to 8%, whereas in RA it is about 12% to 17%, or perhaps even higher. Interestingly, there is an increased prevalence of FM in both systemic lupus erythematosus and psoriatic arthritis. The presence of both RA and FM in the same patient can present a variety of challenges. Through the years, questions have arisen about the validity of disease activity scores and about the appropriate treatment targets in patients affected by both RA and FM. Furthermore, the concept of fibromyalgianess (ie, having characteristics of FM without meeting FM criteria) has been introduced and a study by Wolfe and colleagues showed that, with increasing FM symptoms, clinical variables become more abnormal.

The cause of FM is still unknown. However, it is commonly conceptualized as a stress-related disorder that involves dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. Increasingly, the roles of inflammatory cytokines in FM, central pain syndromes, and psychiatric conditions such as major depressive disorder have been coming to light. Cytokines are known to mediate changes in the HPA axis, and certain clinical symptoms of FM are influenced by cytokines.

Moreover, recent work by Mendieta and colleagues suggests that IL-6 and IL-8 may have a particular significance in patients with FM. These investigators noted that IL-6 is associated with painful events, fatigue, and psychiatric disorders such as depression and stress, whereas IL-8 is associated with pain and sleep disturbances. In their study, the serum levels of interleukin 2, interleukin 4, interleukin 10, granulocyte-macrophage colony-stimulating factor, interferon gamma, and tumor necrosis factor alpha were undetectable in patients with FM and in healthy volunteers. Conversely, the authors found that systemic concentrations of IL-6 and IL-8 increased simultaneously in patients with FM and that both cytokines correlated positively with clinimetric scores. Led by these findings, the investigators concluded that IL-6 and IL-8 might have additive or synergistic effects in the continuous pain that is experienced by patients with FM.

The implications for patients with fibromyalgic RA are, at this point, unclear. The successes of targeting IL-6 in patients with moderate to severe RA have been demonstrated clearly over the years. At the present time, the role of IL-6 signaling (both peripheral and central) in the HPA axis is an interesting and active area of research. Also of interest in fibromyalgic RA is a recent study by Doss and colleagues in which the authors reported an association between seronegative RA and FM, so there seems to be much more to learn about the potentially overlapping pathophysiology, as well.

In conclusion, although the basic science is unfolding, there are many outstanding questions about fibromyalgic RA and its management, as suggested by the Table below. The notion that fibromyalgic RA may be a unique phenotype is not new. However, there continues to be little consensus about the optimal management of patients who fall into this category.