Splenic hypereosinophilia in anaphylaxis-related death: different assessments depending on different types of allergens?

Abstract

The aim of this study was to evaluate splenic eosinophil and mast cell accumulation using pagoda red stain in a series of anaphylaxis-related deaths that underwent medico-legal investigations. Our goal was to assess whether fatal reactions to insect stings, intramuscularly administered antibiotics and intravenously injected contrast media are responsible for specific patterns of eosinophil and mast cell accumulation. Two study groups were prospectively formed, an anaphylaxis-related death group and a control group. Autopsy, histology (haematoxylin-eosin stain, pagoda red stain and immunohistochemistry using anti-tryptase antibodies), toxicology and postmortem biochemistry (beta-tryptase, total IgE and specific IgE) were performed in all cases. All tested parameters (spleen weight, beta-tryptase and total IgE levels as well as eosinophil, mast cell and degranulated mast cell numbers in the spleen) were significantly higher in the anaphylaxis-related death group. No statistically significant differences were observed among the various groups (intramuscular antibiotic injection, intravenous contrast medium administration and stinging insects) in any combination, suggesting that mast cell and eosinophil accumulation in the spleen during anaphylaxis does not have any specific pattern related to the triggering allergen. Despite a lower sensitivity than immunohistochemical staining in discriminating eosinophil and mast cells, pagoda red stain allowed these cells to be identified and could therefore be proposed as a low-cost, first-line diagnostic procedure in those situations where immunohistochemistry is not systematically performed or cannot be carried out.

Vaccination and anaphylaxis: a forensic perspective

“…Activated mast cell and eosinophil accumulation in the red pulp of the spleen has been demonstrated by several authors in anaphylaxis-related deaths using histochemical methods and specific immunohistochemical staining with monoclonal antibodies (44,54,63-66). …”

“…Indeed, samples for histamine determination should be obtained within 15 minutes of anaphylaxis onset, which might only be possible in a small proportion of cases and precluded in most of them. Conversely, samples for mast cell tryptase measurement can be obtained up to several hours after the reaction begins (26,44,46-49). …”

“…Indeed, mast cell tryptase levels can be assessed in postmortem serum even days after death and significantly increased postmortem serum tryptase levels have been reported repeatedly in cases of fatal anaphylaxis (26,44-47,50,51). …”

“…Moreover, beyond cases of fatal anaphylaxis, increased levels of postmortem serum tryptase have been observed in subjects with causes of death unrelated to anaphylaxis. This leads to the conclusion that postmortem, straightforward diagnoses of anaphylaxis cannot be exclusively based on mast cell tryptase determination alone (26,44,45,51-58). …”

“…This means that increased levels do not prove that death was preceded by an IgE-mediated allergic reaction. In addition, similar to mast cell tryptase, increased total IgE levels have been observed frequently in situations unrelated to anaphylaxis, including diseases characterized by immune deficiencies or significant inflammatory components (26,44,45,59,60). …”