Contents

**Preface XI**



Preface

later named tumor necrosis factor-alpha.

mission is now an achievable outcome [5].

failed to materialize.

or an opiate, and sent the patient away without follow-up [4].

I began my career in rheumatology in 1971. As an intern, I took over the rheumatology clinic on Wednesday mornings for indigent patients staffed by an intelligent, recently graduated rheu‐ matologist. He knew all the latest about rheumatic diseases. In hindsight, it was not much.

In those days, we had an anemic treatment arsenal for most rheumatic diseases, including rheumatoid arthritis (RA) that, in fact, barely worked. Antimalarials, parenteral gold, corti‐ costeroids, d-penicillamine, and the relatively new prostaglandin inhibitors such as ibupro‐ fen were included among them [1]. The science of RA was also relatively primitive [2]. We knew that RA was an inflammatory disease, but immunology was in its infancy and consist‐ ed chiefly of T cells, B cells, serum complement, and a few circulating inflammatory pro‐ teins, one of which was associated with malignancy and caused wasting called cachectin,

Even more so for fibromyalgia syndrome (FMS), it was then known as fibrositis. Although a great many etiopathologic hypotheses existed, a "functional condition" was largely consid‐ ered; that is, function was subjectively impaired, but no pathophysiologic abnormalities were evident [3]. Most local practitioners considered it as imaginary, prescribed "a sedative"

Today, we have made fantastic strides in both understanding the pathophysiology and treating RA. We have identified various biochemical players in what we now know to be an extensive, redundant inflammatory cascade and blocked their activity. Remission or near-re‐

Alternatively, although we understand some of the factors that play an etiopathologic role in FMS such as depression, anxiety, helplessness, disordered sleep, and poor physical condi‐ tioning, the biochemistry underlying and connecting these factors remains mysterious [6]. And unfortunately, even when we therapeutically manipulate a few mechanistic factors that we do understand such as serotonin or norepinephrine, the response is very limited [7].

Back in the early 1970s, most RA experts were opposed to the use of antineoplastic drugs or a combination of agents to improve inflammation in rheumatoid arthritis [8]. From my per‐ spective, a rheumatology fellow who was being taught by Art Schebrel to use methotrexate and other cytotoxic agents in 1974 to treat various rheumatic diseases, I learned through contemporary literature, as well as angry calls and letters that the rheumatology community viewed this kind of treatment metaphorically as "A bull looking for a china shop." Antici‐ pated unacceptably, high toxicity was the major issue [9]. Fortunately, those dire prophecies
