Time and change: new dimensions in the immunopathologic spectrum of leprosy

Accumulating evidence of diversity within leprosy types suggests that the traditional application of the concept of an immunopathologic spectrum has been too narrow; new dimensions are necessary to accommodate these observations. The spectrum is a continuous one, not a series of steps, and heterogeneity within each type may be based on factors both inherited ("causal") and acquired ("consequences"). Current clinical and epidemiological data indicate that time is an important variable in several respects. Long increments of time must be considered; major shifts in immune responsiveness from one end of the spectrum to the other may occur in individual patients over many years. The age of onset and duration of illness may generate different risks of immuno-inflammatory reactions in leprosy, also after many years. New methods must therefore be devised to evaluate the immunologic status of patients over several years. The powerful tools of molecular biology and immunology are likely to be more fruitful if applied with new questions in mind to help us understand the diversity within the spectrum and the differing potential for changes in immunologic response over a long period of time.