Amyloidosis: Preliminary Clinical, Chemical, and Experimental Observations*

Although it has been an object of clinical, pathological and, more recently, chemical studies over the course of the past seventy-five years, amyloidosis remains one of the more intriguing enigmas in medicine.As a subject for clinical investigation, this disease is appealing for several reasons.First, it can be produced experimentally in Second, amyloid is accumulated in tissues in sufficient abundance to make its availability for chemical characterization appear a reasonable objective.Third, it is a disease of considerable clinical importance.Thus amyloidosis is a common concomitant of rheumatoid arthriti~;~.' it is a common cause of death of patients with paraplegia, chiefly because of the severe decubitus ulcers and osteomyelitis that often accompany it;8 it is the most important single cause of death of patients with leprosy (unpublished observations, in preparation).I t often accompanies multiple myeloma and, not infrequently, occurs without known predisposing disease, especially in certain Mediterranean countries where two familial forms are indigenous?JO Surely a disease with these characteristics should prove an easy one to understand.This has not proved, however, to be the case.The nature of amyloid is still obscure, the reasons for its diverse origins is unknown, the pathogenesis of none of its forms is understood, and means of its prevention and cure are still uncertain.Approximately six years ago several workers in this laboratory undertook a long-range study of the disease in the hope that what was learned would be helpful in gaining understanding not only of amyloidosis, but also of the even more puzzling diseases of connective tissue that often underlie it.Some of this work has been published, some is in manuscript form, and some is still in progress and permits mention of only the most preliminary conclusions.Nevertheless, as an example of one area in which research in connective tissue is reaching clinical application, a brief and rather general review of the problem may be welcome.Since our studies have been focused along three lines, clinical, chemical, and experimental, it may be helpful a t the outset to emphasize two clinical points.The first pertains to classification.Amyloidosis is often classified into specific types by rather rigid criteria.ll-l*It is said, for example, that "primary" amyloidosis is characterized by predominant involvement of the mesenchymal tissues (blood vessels, skin, heart, tongue, gastrointestinal tract, and nerves), *The investigation reported in this paper was su ported in part by Research Grants A-2123 and .%-lo64from the National Institute of Artintis and Metabolic Diseases, Public Health Service, Bethesda, Md., and grants from the New England Chapter of the Arthritis and Rheumatism Foundation, Boston, Mass., an Institutional Research Grant of the American Cancer Society (IN.42 and 42a) and Eli Lilly and Company, Indianapolis, Ind.This is Publication No. 273 of the Robert W.