Interrelationships of the Mesenchymal Diseases with Consideration of Possible Genetic Mechanisms

Abstract

Review with 426 references. Several of the mesenchymal diseases seem to be related by their occurrence together in the same individual or in various members of the same family. Although certain family constellations suggest that rheumatic fever occurs together with other mesenchymal diseases too frequently to be explained by chance, the sum total of the evidence indicates that rheumatic fever is not related and stands apart from the others. Rheumatoid arthritis and lupus erythematosus are clearly familial diseases as is rheumatic fever, but the operation of a genetic factor, although strongly suggested, has not been established. Further critical evaluation of large twin studies and attempts to establish polymorphisms in these patients must be done. Regardless of the genetic aspects, etiologic factors will be of considerable significance. The streptococcus is clearly etiologically related to rheumatic fever; perhaps other agents as yet undiscovered are as clearly related to other of the mesenchymal diseases. For instance, it is known that certain drugs such as hydantoin and sulfona-mides can induce typical SLE [Systemic lupus erythematosis]. Evidence linking several of these diseases with a disturbed immune response is presented. Study of a striking kindred in which several diseases including agammaglobulinemia, SLE, idiopathic thrombo-cytopenic purpura, and rheumatoid arthritis occurred suggests that altered mesenchymal function, which may be expressed as an altered immune mechanism, may be the abnormally which is inherited. The relationship of abnormalities of thymic structure to the development of aggammaglobulinemia, SLE, a regenerative anemia and pancytopenia, and leukemia is presented. The key role of the thymus in the development of immune responsiveness, and the structural integrity of lymphoid organs is reviewed. It is postulated that disturbances in thymic development may underlie interrealtionships among the several mesenchymal disorders.