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Forensic Science International 198 (2010) e1–e4

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Forensic Science International


journal homepage: www.elsevier.com/locate/forsciint

Case report

Postmortem diagnostics of assumed food anaphylaxis in an unexpected death


S. Unkrig *, L. Hagemeier, B. Madea
Institute of Forensic Medicine, University of Bonn, Germany

A R T I C L E I N F O A B S T R A C T

Article history: Diagnosis of lethal anaphylaxis is known to be difficult to establish in forensic autopsy. Cases of
Received 11 May 2009 anaphylactic shock have to be dealt with in forensic medicine comparatively frequently as death due to
Received in revised form 12 December 2009 anaphylaxis is likely to occur rapidly and without warning in seemingly healthy subjects. Autopsy
Accepted 17 January 2010
findings might hint at allergic reaction, but classic manifestations can also be completely absent.
Available online 2 March 2010
A case of suspected food anaphylaxis in a middle-aged woman is presented. The deceased had been
known to suffer from multiple allergies. Death came about after an evening meal with friends. Dyspnoea
Keywords:
was reported to have been followed by collapse, unconsciousness and death within minutes. The course
Anaphylaxis
Unexpected death
of further analysis undertaken (toxicology, biochemistry, immunohistochemistry) is examplarily
Anti-tryptase described. By means of the results presented we discuss problems and possibilities of postmortem
diagnostics of food induced anaphylaxis.
ß 2010 Elsevier Ireland Ltd. All rights reserved.

1. Introduction of anaphylaxis may die from its implications [6]. Anaphylaxis is


known to result in approximately 18 deaths per year in the U.S.
Anaphylactic shock represents the most severe type of (compared to 2.4 million deaths per year from all causes in the U.S.
anaphylaxis, occurring when an allergic response triggers quick [7]). However, this assumption is clearly an underestimation
release of large quantities of immunological mediators (histamine, [3,4,15]. More cases of sudden death of unclear origin are probably
serotonine, leucotrienes) from mast cells. It is mainly mast cell caused by anaphylaxis, as the most common symptoms include
degranulation leading to systemic vasodilatation that is associated sudden cardiovascular collapse (88% of reported cases of severe
with a sudden drop in blood pressure and oedema of bronchial anaphylaxis) and myocardial causes often will falsely be assumed,
mucosa which results in bronchoconstriction and dyspnoea, especially if an allergic predisposition is unknown to the forensic
urticaria and unspecific gastrointestinal symptoms such as pathologist and the event was not observed by witnesses reporting
abdominal pain, cramps, vomiting, and diarrhoea [4,6,7,14,19]. the patient’s symptoms [3,11,15–17].
Among all illness-related fatalities, deaths from allergic
incidents form a very small subcategory. However, anaphylactic 2. Case history
shock may bring about death within minutes if left untreated. As a
consequence cases of fatal anaphylaxis, though a comparatively We present the case of a 52-year-old woman where the cause of
rare cause of death, have to be dealt with rather more frequently in the unexpected death could not be established by autopsy findings.
forensic pathology than elsewhere, especially if death occurred After a dinner with friends in her own house the lady suddenly
unobserved. Sudden death from natural causes may be nearby, but developed acute dyspnoea, followed by a collapse event and
difficult to confirm. Macroscopic findings as well as conventional unconsciousness. Emergency ambulance arrived 20 min after onset
histopathology are not specific in anaphylaxis [4,7,8,10,19]. of symptoms. However, cardio-pulmonary resuscitation was in vain
An estimated range from 1.24% to 16.8% of the population of the and the patient died.
United States is considered ‘‘at risk’’ for anaphylactic reactions to In the non-smoker’s medical history no diseases explaining a
one or more allergens, especially drugs, insect stings or food sudden death became obvious. The lady’s physical constitution and
contains [1–3]. fitness were reported to have been average although she had been
A great amount of the patients concerned successfully avoid known to suffer from allergies to several food contains and plants.
threatening substances or at least do not progress to severe Guests who had taken part in the evening meal mentioned
anaphylaxis, but up to 1% of those who actually develop symptoms seasonal episodes of bronchial asthma they had observed or been
told about. Diagnostics performed before by the patient’s physician
had evaluated allergic reactions against some plants and food
* Corresponding author. Tel.: +49 288 738363; fax: +49 228 738339. contains, mainly against several sorts of nuts. However, the clinical
E-mail address: Susanne.unkrig@uni-bonn.de (S. Unkrig). symptoms of these allergies seemed to be under control by

0379-0738/$ – see front matter ß 2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.forsciint.2010.01.007
e2 S. Unkrig et al. / Forensic Science International 198 (2010) e1–e4

administration of antihistamines and bronchospasmolytics. Dra- not been capable to establish cause of death but were definitely a
matic episodes of anaphylactic reactions had not been observed hint for fatal anaphylaxis.
before. Immunohistochemistry: Mast cell degranulation is an important
During the postmortem interrogation allergies were mentioned trigger of anaphylactic reactions. At this stage of investigation it
to the investigators and thus became known to the autopsy team. seemed essential to try to make visible acute mast cell
Evaluating possible reasons of death, for instance poisoning, the degranulation in body tissues. Staining of the mast cells with
investigators focused on the contains of the meal served for dinner specific markers (CD 117 and especially anti-tryptase antibodies)
that had taken place shortly before the symptoms’ onset. Dinner was performed. As shown in Figs. 1–3, a lot of preparations mast
had consisted of several courses and the first symptoms seemed to cells were found to have starry sky-like or yard-like distributed
have occurred about two hours after the entree. The meal had material around them. They showed reaction to anti-tryptase in
consisted of crabs, pasta, green salad and white wine. Finally, a the cells but also around the cells in the extracellular space. These
dessert which consisted of almond ice-cream with brownies and
orange liquor (all finished products) had been served about 10 min
before the onset of symptoms.

3. Autopsy/histological findings

The postmortem of the female patient was performed five days


after death, the delay due to administrative reasons. Macroscopical-
ly glassy, partly tough mucus in the bronchi, dilatation of right heart
chamber and right atrium, petechial bleedings in the conjunctivae,
petechiae of the pleura, liquid blood, cyanotic discoloration of nail
beds, stool and urine outlet were found, as well as bilateral rib
fractures, several of these findings obviously caused by the attempt
of cardio pulmonary resuscitation. Oedema of the glottis, urticaria or
other skin reactions typical in allergy were not found.
There was no sign of pulmonary embolism or relevant
arteriosclerosis. Evidence of heart disease or other potentially
lethal illnesses could not be found, either. Fresh injuries – apart
Fig. 1. Mast cells, throat, anti-tryptase, 200.
from the rib fractures mentioned that did not show vital reactions
– were absent. Identifiable components of stomach content
matched the information available about the meal consumed
before death and appeared similar to some leftovers in the kitchen.
Histological examination of the lungs showed mild thickening
of the basal membranes of the lungs and some interstitial and
alveolar oedema. Cerebral oedema, that had been diagnosed
macroscopically, was observed as well. In summary, routine
histological examination did not reveal potentially lethal findings.

4. Further investigations: toxicology, biochemistry,


immunohistochemistry

An overall toxicological analysis of blood samples collected


during postmortem revealed no evidence of poisoning. Medium
blood alcohol concentration was 0.13%. Intake of benzodiazepines
and any other common pharmaceutics, cocaine, morphine and
analogues, amphetamines and designer drugs was excluded by
immunochemical analysis and screening by high performance Fig. 2. Mast cells in lung tissue, CD 117, 400.
liquid chromatography coupled with mass spectrometry.
Postmortem IgE tests brought forward a high titre of IgE
antibodies (134 kU/l) in the patient’s blood. The standard range of
IgE was indicated <100 kU/l for adults by the analysing laboratory.
Further tests revealed moderately increased to very high concen-
trations of specific IgE against cat epithelia, horse and dog sheds,
hazel nuts, almonds, apple, rye, wheat, alder and birch tree antigens.
Additional tests for serum tryptase concentrations demonstrat-
ed a high serum level of the enzyme of 12.5 mg/l. The normal range
of tryptase in serum, i.e. the reference value in healthy individuals,
is indicated in literature between 5.6 and 9.8 mg/l (a value of the
90th percentile). Tryptase concentration in the patient in question
had never been measured before; therefore an acute rise of the
enzyme blood concentration – due to mast cell degranulation and
pathognomonic in anaphylaxis – could not be proved beyond
doubt. It goes without saying that in contrast to living persons the
patient’s individual basic tryptase level could not be evaluated ex
post. As a whole, forensic and biochemical findings had, up to then, Fig. 3. Mast cell degranulation, lung tissue, anti-tryptase, 400.
S. Unkrig et al. / Forensic Science International 198 (2010) e1–e4 e3

immuno-histological findings are compatible with an acute


degranulation of mast cells indicating an acute systemic reaction
triggered by allergy [11,16].
Anaphylaxis was henceforward presumed as cause of death of
the patient in question.

5. Discussion

Tryptase is a protease secreted by degranulating mast cells in


blood and interstitial space. Therefore, the degree of activation and
degranulation of mast cells during acute allergic reaction, which
leads to a sudden release of larger quantities of this enzyme and
other mediators, can be estimated by measuring the amount of
tryptase in blood, especially as other sources of serum tryptase are
of negligible relevance [5,12,13]. There is a wide range of normal
values of tryptase and IgE in healthy individuals though, a fact that
may render diagnosis of acute anaphylaxis rather difficult even Fig. 4. Intestinal mucosa, anti-tryptase, 100.
among clinical cases unless basic values from recent examinations
are accidentally at hand [9,11,12]. Results on tryptase levels in
cadaver blood may not be relied upon to the same degree of delayed); on the other hand, elevated basic levels of tryptase are
evidence as in clinical examination mainly because of the influence assessed for instance in patients with mastocytosis [17]. Therefore,
of autolysis [16]. In other words, the relevance of tryptase levels in a single elevated measurement of tryptase concentration may
blood samples taken from cadavers is not quite as reliable as that of contribute to the diagnosis of anaphylaxis, however, there are
patients alive [6,9,11,16]. difficulties of interpretation [9,17]. Only very high postmortal
Diagnosis of anaphylaxis as a cause of unattended sudden death values of tryptase are accepted in literature as pivotal for a death
in forensic medicine means diagnosis by exclusion [10]. There may resulting from an anaphylactic reaction [8,17,18].
be a few hints leading to the right clue among autopsy findings, such In the case discussed here, tryptase results indicated mast cell
as oedema of the glottis, urticaria or swellings, these findings, activation, however, with a geometrical mean value of tryptase in
however, being neither specific nor essential [8,19]. Case history serum between 5.6 and 9.8 mg/l (a value of the 90 percentile) this
may also lead to suspected anaphylaxis, but especially in forensic result of measurement lay still evenly within the scattering range
fatalities, even in patients with well-known severe systemic of the normal distribution.
allergies it is essential to obtain additional evidence [11]. In clinical An extraordinary degree of mast cell degranulation could be
cases, diagnosis may be supported by a rise of serum tryptase within demonstrated by immunohistochemistry. Vacuolar accumulation
hours after the acute event [14]. According to literature, very high of anti-tryptase positive material near mast cells was interpreted
postmortal values of tryptase are interpreted as significantly pivotal as sign of degranulation. Anti-tryptase positive material was found
for a death resulting from an anaphylactic reaction [8,11,16]. scattered close to mast cells. Remarkably, mast cell breakup had to
In the case presented here, macroscopical findings, observed be suspected not only in the intestine (Fig. 4), but also in lung tissue
symptoms and facts from the patient’s medical history gave reason and throat mucosa.
for a high-grade suspicion of anaphylactic shock as cause of death Advanced autolysis might limit the significance of immuno-
[8,9,10,11,16]. The observed relationship between the intake of the histological findings and cannot be completely excluded as a
dessert containing nut allergen and the start of symptoms further potential factor of interference. Nevertheless, the histological
strengthened this presumption [1,2,3]. However, the macroscopic findings in synopsis with the reported symptoms and the intake of
findings did not permit a clear diagnosis [8,19]. food known to be allergy-associated seemed qualified to enhance
Crab meat and other contains of the main course were the evidence and confirm suspicion of an anaphylactic shock as the
discussed as potential sources of food allergy, the time course cause of death in this woman.
and anamnestic information about allergic reactions on nut In case of suspected death from anaphylaxis autopsy should be
antigens, however, mainly led to further analysis of the ingredients carried out as soon as possible in order to allow a valid diagnosis.
of the dessert, which consisted of almond ice-cream with brownies Apart from chemical parameters like tryptase immuno-histological
and orange liquor (all finished products). From the declaration of methods provide a valid contribution to the verification of
ingredients of the almond ice-cream traces of peanuts, other sorts anaphylactic reactions as cause of death. As the case presented
of nuts, egg and soy were also identified as possible antigens. shows the combination of anamnestic information, autopsy findings,
Even at average ambient temperature, the total amount of IgE tryptase determination and immunohistology can help to make
antibodies in a corpse is considered relatively stable after the likely an anaphylactic reaction as cause of death in patients dying
individual’s death and can be regarded a reliable allergy-associated suddenly with unspecific symptoms [9,10,11,16,17].
parameter. IgE result and specific IgE values characterized the Limitations resulting from postmortal changes following
patient’s pathological immunological reaction [5]. The high advanced autolysis have to be kept in mind when interpretation
amount of entire IgE antibodies indicated the lady’s highly allergic of single findings is performed. Tryptase level in serum of cadaver
disposition. IgE increase alone, however, can naturally not be blood can be misleading or on the other hand may be confirmed by
regarded proof of anaphylaxis [5,13]. immunohistology with CD 117 or anti-tryptase antibodies [11,16].
Though after consideration of all postmortem biochemical
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