[Historical review of rheumatology and future directions]

Rheumatic diseases are suggested to be recognized 2400 years ago, but little progress had been made in distinguishing specific diseases until the 17th century. After the two decades, the concept of rheumatic diseases was established and followed by the new concept of autoimmune diseases in the 20th century. Many key drugs for rheumatic diseases, such as glucocorticoids and immunosuppressants, were developed in the 1940s and 1950s. Their effect, toxicity and limitations have been investigated for fifty years. On the other hand, new treatment strategy was developed. Advances in genetics and molecular cell biology in the 1980s brought us the discovery of many cytokines and chemokines and elucidated the role of these molecules in autoimmune diseases. These progresses have led to the development of a number of biological agents for the rheumatic diseases during past decade. Among these drugs, TNF blockade showed the remarkable effectiveness in rheumatoid arthritis and this success indicated the new treatment era. However, compared to the simplicity of target molecules in monoclonal antibody therapy, biological effects are more complex. Therefore, we must keep in mind the possibility of the appearance of unexpected adverse effects such as TGN1412. This review presents a history of rheumatology and discusses future directions of basic and clinical research for rheumatic diseases.