Shwartzman phenomenon

Shwartzman phenomenon
Other names	Shwartzman reaction, Sanarelli-Shwartzman reaction
Specialty	Hematology
Causes	bacterial endotoxin

Shwartzman phenomenon (also known as the Shwartzman reaction and the Sanarelli-Shwartzman reaction) is a rare reaction of a body to particular types of toxins, called endotoxins (lipopolysaccharides in particular). The endotoxins cause the immune system to overporoduce cytokines which leads to thrombosis in the affected tissue. A clearing of the thrombosis results in a reticuloendothelial blockade. which prevents re-clearing of the thrombosis caused by a repeat introduction of the toxin. That will cause tissue necrosis. Shwartzman phenomenon is usually observed during delivery or abortion, when foreign bodies are introduced into the tissues of the female reproductive system.

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 ^[1] and observed that after injecting a small dose of Bacillus typhosis (currently known as Salmonella enterica serovar Typhi into the skin of rabbits as a "priming dose" and then following 24 hours later with an intravenous injection of the same toxin caused a hemorrhagic necrosis in the original injection site in the skin. He then repeated the experiments to find that this phenomenon also occurred when using the solution obtained after filtering the live bacteria out from the solution (culture filtrate). ^[2]

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

The phenomenon begins with a "priming" event. This generates a hypersensitive innate immune response to the antigen, typically this antigen is an endotoxin (e.g. lipopolysaccharide) from gram-negative bacteria. This activates the innate immune response which releases the pro-inflammatory cytokines IL- 1 ^[3] , TNF ^[4] , IFN-γ, and IL-15.

The second dose of this "two-hit" model is known as the "provocative" dose. This must be timed within a narrow window between 2 and 24 hours. The effect of this dose is to cause a deposition of fibrin material and platelets within the lumen of the capillaries causing coagulation and obstruction of the blood vessels. Lack of oxygen causs the surrounding tissue to die and turn necrotic.

Syndromes involving the Shwarzman reaction include: purpura fulminans, meningococcemia and septic shock

References

1. Chahin AB, Opal JM, Opal SM (November 2018). "Whatever happened to the Shwartzman phenomenon?". Innate Immunity. 24 (8): 466–479. doi:10.1177/1753425918808008. PMC   6830869 . PMID   30409091.
2. Gregory Shwarzman. "Studies on Bacillus Typhosis Toxic Substances. I. Phenomenon of Local Skin Reaction to B. Typhosus Culture Filtrate". Journal of Experimental Medicine. 48 (2): 247–268. doi: 10.1084/jem.48.2.247 . ISSN   1540-9538.
3. Movat HZ, Burrowes C, Cybulsky M, Dinarello C. (1987). "Acute inflammation and a Shwartzman-like reaction induced by interleukin-1 and tumor necrosis factor. Synergistic action of the cytokines in the induction of inflammation and microvascular injury". Am J Pathol. 129 (3): 463.
4. Piguet P, Grau G, Vassalli P. "Subcutaneous perfusion of tumor necrosis factor induces local proliferation of fibroblasts, capillaries, and epidermal cells, or massive tissue necrosis". Am J Pathol. 1990. 136 (1): 103.