Vaccinia necrosum and its relationship to impaired immunologic responsiveness

Abstract In a sixty-four year old man with hypogammaglobulinemia (depressed immunoglobulins G, A and M) related to chronic lymphocytic leukemia, vaccinia necrosum developed following smallpox vaccination. Initially, neither circulating neutralizing antibodies nor specific cellular immunity (delayed hypersensitivity) to vaccinia virus was measurably present; however, following administration of vaccinia immune globulin (VIG), cellular immunity was restored and clinical recovery ensued. This patient's illness and a review of previously reported cases suggest that the major defect responsible for the development of vaccinia necrosum in man is a simultaneous depression of circulating neutralizing antibodies and of cellular immune responsiveness, and that recovery from vaccinia necrosum depends upon development of cellular immunity. In this process, circulating neutralizing antibodies appear to establish a necessary balance between viral antigens and the cellular immune system, thus "freeing" what appears to be a "paralyzed" immune system. It is suggested that the therapeutic effect of VIG is via this mechanism. A schematic diagram outlines the various immunologic defects that may result in vaccinia necrosum, and possible patterns of host response.