Shwartzman phenomenon
Shwartzman phenomenon is a rare hyperimmune reaction of the body to toxins associated with bacteria.
History
In 1923, Gregory Shwartzman, a doctor at Mount Sinai Hospital in New York City was trying to understand the Arthus reaction in terms of bacterial endotoxins and observed that after injecting a small dose of Bacillus typhosis. The culture filtrate contained the toxic lipopolysaccharide endotoxins from Salmonella typhi.Four years before Shwartzman published his paper, a controversial Italian researcher named Giuseppe Sanarelli described a similar phenomenon using culture filtrates from Vibrio cholerae.
Description
In the experiment by Shwartzman, the phenomenon begins with a "priming" event. The initial injury of the skin is combined with the introduction of strong antigens inititate the innate immune response. Stimulated by the toxins, macrophages release cytokines both mast and defensive white blood cells rush to the injection site to fend off bacterial invaders.The second dose of this "two-hit" model is another injection of toxin, but this time delivered intravenously and known as the "provocative" dose. This must be timed within a narrow window between 2 and 36 hours after the priming dose. The timing is to coincide with presence of the activated white blood cells in the tissue at the site of the priming dose.
The massive neutrophil infiltration at the priming injection site releases the pro-inflammatory cytokines IL- 1, TNF, IFN-γ, and IL-15. Complement is activated and a deposition of fibrin and platelets within the lumen of the capillaries leads to coagulation and obstruction of the capillaries at the site of the priming injection. This culminates in a lack of oxygen which in turn causes necrosis of the surrounding tissue. The skin at the injection site turns blue and then purple as the necrosis progresses.
The phenomenon can be local or generalized. The generalized Shwartzman reaction serves as an experimental model for disseminated intravascular coagulation.