The role of protein malnutrition in the pathogenesis of ulcerative "Lazarine" leprosy.

1. Clinical and necropsy observations in lepromatous leprosy associated with severe emaciation and accompanying hypoproteinemia suggest that protein deprivation may be of pathogenic significance in the ulcerative phenomenon that is designated "Lazarine leprosy". 2. An experimental utilizing Wiersung rats infected with Mycobacterium lepraemurium and maintained on a protein-free diet was developed for the purpose of studying the effect of protein starvation on the course of chronic mycobacterial disease similar to lepromatous leprosy with respect to pathogen and host inflammatory response. 3. It was possible to maintain the experimental animals on a protein-free diet for up to 18 weeks of concomitant M. lepraemurium infection. This was long enough for the infection to disseminate to a degree that was evident in control animals only several weeks later. 4. The protein-deprived animals showed decreased inflammatory response to the pathogen, presented more rapid dissemination of the infection and harbored more bacilli per macrophage than did animals similarly infected but maintained on a protein adequate diet. This indicates impairment of native cellular immunity by protein deprivation through decrease in ability of macrophages to inhibit bacillary multiplication. 5. There was no evidence of impairment of macrophage ability to phagocytose the pathogens. 6. Morphologically the increased dissemination of pathogens and decrease in inflammatory response was similar to the increase in number and extent of visceral lesions seen in Lazarine leprosy. Decreased ability to dispose of the infecting bacilli was similar in the two models, human and animal. The animal model does not, as does lepromatous leprosy, involve the skin in the infection. Hence comparable ulcerative phenomena were not replicated in the animals. 7. It is suggested that Lazarine leprosy may result from enhanced lepromatous leprous infection occurring as a result of protein malnutrition. The pathogenic mechanism appears to be impairment of cellular immunity probably enhanced by concomitant impairment of humoral antibody immunity resulting also in decreased resistance to pyogenic and other secondary pathogens. The tissue edema attendant on decreased serum osmotic pressure due to lowering of the serum protein fractions enhances the probability of ulceration.