A question, Herein lies part of the problem. We have no difficulty identifying so-called classical rheumatoid arthritis but there is a larger group of patients who do not exhibit the classical features. There is clinical heterogeneity within this latter group. It includes (1) patients exhibiting intermittent arthritis with little or no residua between attacks, ( 2 ) patients with sustained inflammatory disease involving a limited small number of joints, and ( 3 ) patients with rheumatic manifestations which are barely symptomatic who possess certain rheumatoid features, i.e., "rheumatoid factor" or rheumatoid nodules. According to current criteria, most patients with 6 weeks or more of objective arthritis in two or more joints, who do not exhibit evidence Qf an alternative basis for the manifestations, are labeled with the diagnosis of rheumatoid arthritis (RA). At the outset, it must be admitted that etiologic bases for this clinically heterogeneous group of disorders may be diverse.
(By analogy, hepatic cirrhosis can have as its basis primary disturbances involving nutrition, viral infection, schistosomiasis, and copper or iron metabolism; yet a singIe etiologic agent such as the Treponema pallidurn may result in a variety of clinical syndromes.)
This presentation is an effort to examine the existing knowledge which, in the author's opinion, will most likely lead to the elucidation of the pathogenesis of RA. Features of RA which will influence the discussion' are listed below. Any etiologic concept offered must provide explanations for the majority of the phenomena.
B. FEATURES
OF RA WHICH MUST BE RECONCILED WITH ETIOLOGIC HYPOTHESES 1. Common disease (1.24 per cent with "definite" or "probable" RA in Tecumseh, Mich. ) From the Department of Mcdicine, Columbia University College of Physicians and Surgeons, and the Edward Daniels Faulkner Arthritis Clinic of the Presbyterian Hospital, N e w York, N . Y.