Networked Knowledge - Medical Issues
Issues Relating to Allergies, Anaphylaxis and Sudden Death

Authors: Dr (a lawyer not a medical doctor)Robert N Moles and Bibi Sangha barrister

We are grateful to Dr Richard Pumphrey (UK), Professor Malcolm Fisher (Australia) Associate Professor Tony Thomas and Dr Byron Collins for their assistance

An allergy is an inappropriate or excessive immune response to antigens.

An antigen is a substance that stimulates the production of antibodies when introduced into the body.

A toxin is therefore one type of antigen.

The sudden increase in cellular activity or antibody titres (concentration) can have a number of unpleasant side effects.

Neutrophils or cytotoxic T cells may destroy normal cells while attacking the antigen. The antigen-antibody complex may trigger a massive inflammatory response.

Antigens which trigger allergic reactions are often called “allergens”.

Immediate hypersensitivity begins with the process of sensitisation, which is the initial exposure to an allergen that leads to the production of antibodies, specifically large bodies of IgE (Immunoglobin E). The tendency to produce IgE antibodies in response to specific allergens may be genetically determined.

There is a time lag in the process needed to activate B cells, produce plasma cells, and synthesise antibodies. Because of this it might well be the case that the first exposure to the allergen does not produce symptoms. It simply prepares the system for the next exposure stage.

However anaphylaxis to some drugs commonly occurs on first exposure and this is probably related to sensitivity being acquired from another substance of similar structure.

After sensitisation, the IgE antibodies become attached to the cell membranes of basophils and mast cells throughout the body. When there is a further exposure to the same allergen, the bound antibodies stimulate these cells to produce histamine, heparin, several cytokines, prostaglandins and other chemicals into the surrounding tissues.

A sudden massive inflammation of the affected tissues results.

The cytokines and other mast cell secretions draw basophils, eosinophils, T cells and macrophages to the area. These cells then release their own chemicals, extending and exaggerating the responses initiated by the mast cells.

The severity of the allergic reaction depends on the individual’s sensitivity and the location involved. If allergen exposure occurs at the body surface, the responses may be restricted to that area. If the allergen enters the bloodstream, the response could well be lethal.

Anaphylaxis

A circulating allergen affects mast cells throughout the body. Changes in capillary permeabilities enable the clear fluid in the blood (plasma) to leak out into the surrounding tissues. This produces what we see as swelling and oedema (excess fluid) in the dermis (the skin). This appears as raised welts, or hives which appear on the surface of the skin. Smooth muscles along the respiratory passageways contract. The narrowed passages make breathing extremely difficult. In severe cases, extensive peripheral vasodilation occurs [vaso = blood vessels: dilation = expands] producing a fall in blood pressure which can lead to circulatory collapse.

Treatment

Many of the symptoms of immediate hypersensitivity can be prevented by the prompt administration of antihistamines. These drugs block the effect of the histamine which has been released. Benadryl (diphenhydramine hydrochloride) is a popular antihistamine available over the counter. The treatment of severe anaphylaxis involves antihistamine, corticosteroid and epinephrine injections. [Martini Fundamentals of Anatomy and Physiology 5th edition pp788-789].

However, the administration of intravenous fluids, oxygen and artificial ventilation are all more important than antihistamines and steroids.

Anaphylaxis may occur rapidly or slowly. In minor reactions or progressing reactions antihistamines may prevent progression but in severe or rapidly occurring reactions antihistamines alone will not prevent reactions nor be effective treatment. In these cases adrenaline and intravenous fluids are necessary plus artificial ventilation if asthma occurs and intubation (passing a tube into the trachea) may be necessary for airway swelling.

Schulz says that systemic anaphylaxis is an acute allergic reaction characterised by an appearance of a generalised flush, weakness, anxiety, dizziness, palpitations, tingling of the extremities or of the tongue, urticaria (nettle-rash), angiodeama nausea and vomiting, uterine and gastro intestinal cramps, within a few minutes of administration of the drug or any particular allergen to which the individual is sensitive.
[Schultz KM Dermatology p100].

It is usual for reactions to injected or inhaled antigens to occur rapidly and those to ingested antigens more slowly - but reactions to ingested antigens may occur within minutes.

If not treated the reaction may progress to skin rashes, respiratory distress, swelling of face, airway, or whole body, hyper-peristalsis cardiac arrythmias, cardio vascular collapse, abnormal blood clotting, coma and death.

Anaphylactic symptoms are commonly produced by parenteral injections (administered or occurring elsewhere than in the alimentary canal). This could be for example an injection into the muscles of the arms or legs. However, it is more commonly due to bees, wasps, ants and peanuts.

However, in highly sensitive persons oral, percantaneous, vaginal and even respiratory exposure may produce a similar response.

Examples have been cited of sensitised persons developing the reaction by merely being in a restaurant where the allergen has been included in a “sizzling” dish. The Australian Society for Clinical Immunology and Allergy states that 1 in 200 babies are affected by peanut allergies. “But some develop a potentially deadly condition known as anaphylaxis. In these cases death can occur within minutes.” [The Australian  22 March 2002 “Peanut butter snack proves deadly for boy”. Reports how a 13 year old boy died of a cardiac arrest shortly after eating a spoonful of peanut butter].

Anaphylaxis can in most instances be distinguished from vaso (blood vessels) vagal (nervous system) syncope. This is a transient vascular and neurogenic reaction marked by pallor, nausea, sweating, bradycardia (heart slows below 80 beats per min) and a rapid fall in arterial blood pressure.

In anaphylaxis, the patient develops a flush (usually a transient redness of the face and neck) and tachycardia (heart races above 110 beats per minute) in contrast to the blanching diaphoresis (profuse perspiration) and bradycardia associated with vaso-vagal reactions. Vagal inhibition means that the nervous system causes a systemic shutdown or shutdown of the autonomous systems such as the heartbeat and breathing.

In anaphylaxis, symptoms usually develop within seconds or minutes reaching a maximum within 5 to 20 minutes for injected antigens. The reaction is much more variable and likely to be slower for ingested or topical antigens. In a drug induced allergy, the reaction is most likely to occur at the start of a new course of treatment, with a previously used drug which may not have caused allergic symptoms at earlier times. Anaphylactic  hypersensitivity can also persist for many years in the absence of any known exposure to the drug.

Death is usually due to hypotension which involves a dilation of the blood vessels. Clearly alcohol would compound this effect, as would a hot bath also. Laryngeal oedema, cardiac arrest or bronchospasm may also occur and contribute to death because of the failure of oxygen delivery. 

In the Keogh case, it was said that the airway of the deceased was blocked with vomitus material. The inability to obtain an airway could also have been caused by blockage of the airway which could result from muscular spasm of the larynx or bronchial muscles which would have been undetectable at post mortem. The obstruction of the airway could also have been caused by laryngeal oedema and the inhalation of vomitus material. It is clearly possible that death in this case could have been due to the aspiration of vomit. Vomiting occurs in 10-15% of patients with anaphylaxis.

Schulz states that in 50 post mortems of patients who died of anaphylactic shock, lesions were restricted in 70% of the cases to the upper respiratory tract, which was obstructed by intense oedema and secretions, although this is not confirmed by the findings of Pumphrey, Delage and Irey.

In some cases, diffuse vascular lesions were associated with congestion of the liver and kidneys, thrombosis of the coronary arteries and haemolysis.

Haemolysis involves the bursting of the red blood cells so as to release the red pigment in the cells which then stains the lining of the blood vessels. The cells can burst in this way owing to excess fluid which might result from the sudden intake of water, or from oedematous activity.

We must bear in mind that haemolysis was said to have been found at autopsy in the Keogh case, although it was explained as part of a process of “drowning”. As we can now see from the previous paragraph, whilst haemolysis is consistent with drowning, it is also consistent with the severe vascular reactions found in anaphylaxis.

Apart from severe cardio-vascular collapse which is found in anaphylactic shock, all of the symptoms may occur in a milder form such as generalised urticaria (a rash), skin allergy, angioneurotic oedema (angioedema) and asthma attacks.

At autopsy in the Keogh case we understand that there were indications of acute (rather than chronic) asthma in Anna Cheney’s lungs at the blood cell level. In general, the faster the symptoms appear after an injection or ingestion of a drug, the more severe the reaction.
[ Schulz KM Dermatology p101].

A number of substances appear to induce systemic (full body) reactions which may closely resemble an IgE mediated anaphylactic shock, but which are due to different patho-physiological mechanisms. Such reactions are generally denominated “anaphylactoid” – the clinical resulting reaction being one and the same. According to Bruinsma 1972, who evaluated 50,000 notifications of adverse drug reactions of every conceivable kind, roughly one quarter of all side effects were associated with skin changes. Most of these were urticarial and macro-papilar eruptions.
[Schulz KM Dermatology p103].

The medical world is becoming much more concerned about the prevalence of anaphylactic reactions and the extent to which they have not previously been recognised as such.
[ “Post mortem findings after fatal anaphylactic reactions” Richard SH Pumphrey and Ian SD Roberts, Immunology Unit, Central Manchester Health Care, St Mary’s Hospital, Journal of Clinical Pathology April 2000 vol 53(4) pp273-276].

Pumphrey and Roberts’ Report

Pumphrey and Roberts conducted an interesting series of studies which were written up in “Post mortem findings after fatal anaphylactic reactions” in the Journal of Clinical Pathology, April 200. The following discussion is taken from that article.

A register has been established in the UK since 1992 of fatal anaphylactic reactions, traced from the certified cause of death and other sources.

Details of the previous medical history, and the reactions, suggests anaphylaxis as a cause of death for 130 cases.

A post mortem report was available for 56 of them.

Of those, 19 of the reactions were due to wasp venom, 16 to foods and 21 to drugs or contrast media. (Contrast media = injections for X rays etc).

Death occurred within 1 hour of the anaphylactic onset in 39 of the cases.

Macro findings included signs of asthma, mucous plugging and or hyper-inflated lungs in 15/56.

Petechial haemorrhages were found in 10/56.

Pharyngeal or laryngeal oedema were found in 23/56.

However, in 23/56 there was nothing indicative of an allergic death.

Mast cell tryptase was raised in 14/16 cases tested.

It is clear that in many cases of fatal anaphylaxis, no specific macroscopic findings are present at post mortem examination. This reflects the rapidity and mode of death, which is often the result of shock, rather than asphyxia.

The investigations that might have helped determine whether anaphylaxis was the cause of death had rarely been performed.

In the presence of a typical clinical history, the absence of post mortem findings does not exclude the diagnosis of anaphylaxis.

Additional symptoms of anaphylaxis include conjunctivitis and rhinorrhoea (running nose) sneezing and coughing and loss of consciousness from shock or breathing difficulty caused by upper or lower airway resistance.
[Upper airway = larynx, throat. Lower airway = bronchioles and smaller air sacs in the lungs].

More severe reactions can lead to respiratory or cardiac arrest.

Asphyxia can follow:

1. upper airway obstruction as result of pharyngeal or laryngeal oedema

2. lower airway obstruction as result of bronchospasm due to the smooth muscle in the airways responding to histamine

3. mucus plugging which is where the mucus is being produced at a faster rate than its removal, and causes blockage.

In the airways, there are cilia which are the fine, frill-like extensions from the tissue, which transport the mucus through a rippling effect.

Cardiac arrest can follow respiratory arrest or occur with respiratory difficulty. As result of either, the direct effects of the mediators of anaphylaxis on the heart, or the profound shock, resulting from peripheral vasodilation, often combines with angiodeama causing loss of intravascular fluid.

In cases where this shock is established within minutes of the start of the reaction, there may be no time for other features to occur.

Pumphrey and Roberts state that in their study of fatal anaphylaxis, they encountered cases where, despite a convincing clinical history, anaphylaxis had been rejected as a cause of death, because of the lack of specific findings at post mortem.

It must be understood that the mode of death is not the same for each cause. However what was found was that:

All food-allergic reactions caused difficulty in breathing that led to respiratory arrest in 13/16 cases.

Shock without difficulty in breathing was more common in venom 8/19.

Iatrogenic reactions were 12/21.

Anaphylactic deaths can be confused with bronchitis etc, and may only be diagnosed properly after having conducted a tryptase test. Tryptase is a protein not normally found in blood-serum, and is only found in the serum and tissue after degranulation of the mast cells.

The mast cells contain granules and when the cell degranulates, it loses its membrane and the granules are freed. This causes a release of histamine into the vascular system and into the tissue. The histamine function is to dilate the blood vessels. This allows the white cell reaction to speed up, which it needs to do when there is an infection. However, if this process gets out of control, the oversupply of histamine causes a loss of blood pressure.

In addition, the histamine may also cause the smooth muscle to spasm and this causes the airways to contract. As already mentioned, this combination of loss of circulatory pressure and breathing difficulties, can cause the cessation of either or both systems.

Of the post mortem findings, the most common was:

Non specific pulmonary congestion and oedema which was present in 41 or 73% of the cases.

Features suggesting an allergic reaction were present in 59% of cases.

This was sub-divided into 100% of immediate deaths in food, 67% of deaths by venom and 37% from the iatrogenic groups. 

Cutaneous erythema and urticaria were found in only three of the post mortems. However, a possible explanation for this is that by the time of the post mortem examination (especially where it has been delayed as in the Cheney case), any cutaneous oedema and urticaria might well have been absorbed back into the system.

Sir Bernard Knight (the well known British pathologist) says he has never seen such signs at post mortem.

Laryngeal and pharyngeal oedema were found in 23 deaths. This was sub-divided into 8% laryngeal and 49% pharyngeal of the immediate deaths.

Upper airway oedema was more common in the deaths related to food, some 77%.

Those occurring after reactions with venom or drugs came to 40% and 30% respectively, of immediate deaths.

Hyperinflation of the lungs or mucus plugging of the airways, suggesting an asthmatic component were found in 15 cases, 13 of which were immediate deaths.

Brain swelling, suggestive of cerebral hypoxia was found in 15 cases of which 7 were delayed deaths.

Histology was performed at 20 post mortems, and in 2 cases they showed airway oedema. The histology of the laryngeal mucosa demonstrated a pronounced eosinophilia. The histology of the bronchii demonstrated mucosal oedema, inflammation with eosinophilia and epithelial sloughing in three of the four cases with mucous plugging identified macroscopically. Serum concentration of mast cell tryptase was documented in only 16 of the post mortems. Of these, concentrations were raised in 14. In the 2 cases where tryptase was not raised, death was delayed by 8 and 480 hours. (This may suggest that the tryptase has been metabolised back into the system)

The authors found that in 23/56 anaphylactic deaths studied there were no macroscopic post mortem findings suggestive of anaphylaxis.

Mast cell tryptase – mast cell (beta) is a protein released from mast cell granules during anaphylactic reactions. (Alpha) tryptase is a similar protein that is secreted by resting mast cells and is raised in mastocytosis (abnormal amounts of mast cells).

The test for mast cell tryptase has been available in the UK. Before 1997 it detected beta tryptase – and since then the most widely used test does not distinguish between the alpha and beta. Beta is reasonably stable in serum over a period of days and therefore can be measured in post mortem samples.

The authors conclude that in many cases of fatal anaphylaxis, no specific findings are present at post mortem. As explained, this is particularly likely with those reactions which cause a rapid onset of shock.

In the presence of a typical history, the absence of specific findings at post mortem, does not exclude a finding of anaphylaxis. Tests for specific IgE and mass cell tryptase might help to determine if anaphylaxis is the cause of death, but it is not often used.

Pumphrey and Roberts therefore recommend these tests should be performed in all cases, with a suggestive clinical history, with no specific findings at post mortem.

Furthermore, the possibility of anaphylaxis should be considered in ALL cases of sudden unexpected death, with absent post mortem findings. The femoral vein blood should be sampled, and the separated serum frozen, to enable later testing of specific Ig antibodies and mast cell tryptase.

The results of these assays should be interpreted in the context of the clinical history and post mortem findings. Because interpretation is often difficult, specialist immunological advice should be sought.

NSAIDs

Another interesting study was reported in the article “Anaphylactoid reactions due to non-steroidal anti-inflammatory drugs” in Clinical and Cross Reactivity Studies – Annals of Allergy, Asthma and Immunology. [Vol 78 March 1977 pp293ff  J Quiralte C Blanco R Castillo Nancy Ortega and Teressa Carrillo]

This study found that drugs are the most common cause of anaphylaxis.

The authors pointed out that in different epidemiologic surveys, non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently encountered drugs. In the study, an anaphylactic reaction was defined as the presence of urticaria and / or angiodeama plus hypotension (where the systolic blood pressure was below 90mm mercury) and / or laryngeal oedema.

For the purpose of the study, subjects were diagnosed as being atopic if they met the following criteria (those criteria included rhinitis, conjunctivitis and bronchial asthma).

The study found that anaphylactic reactions were more common in women. It stated that NSAIDs as a group have been associated with an increased relative risk for anaphylactic reactions. The authors took the view that drug sensitivity usually coexists with an underlying disease such a rhinosinusitis and or bronchial asthma and chronic urticaria. 

HJ Schwartz, JW Yunginger and LB Schwartz stated the important question in the title of their article, “Is unrecognised anaphylaxis the cause of sudden unexpected death”? 
[Clinical and Experimental Allergy no 25 pp866ff].

They stated that serum tryptase levels reflect mast cell activation and correlate with anaphylactic reactions. Elevated post mortem tryptase levels have been found in witnessed fatal anaphylaxis.

They explained that anaphylaxis is the clinical expression of a systemic, immediate, hypersensitivity reaction, conditioned by the release of the mediators of inflammation from mast cells and possibly basophils. Anaphylaxis can result from direct immunological activation of these cell types or can be idiopathic.

Serum tryptase levels rise after non-fatal anaphylaxis induced by a bee sting, and reach a peak from 30 mins to 1 hour after the sting and then declines with a half-life of about 2 hours. Elevated mast cell tryptase levels range equals 12 to 150,000ng per ml have been observed in serum samples obtained pre-mortem or up to 24 hours post mortem from 17/19 cases of witnessed anaphylaxis. 

The authors expressed the view that a sudden and unexpected cause of death may be caused by anaphylaxis more often than is currently recognised. They say that at a minimum they have shown that mast cell tryptase can be detected in post mortem sera that have been stored at minus 20 for over 10 years.

Evidence of substantial mast cell activation tryptase level 10 or greater ng per ml was present in 9/68 – some 13% of sudden and unexpected deaths, despite the sera having been collected in a less than ideal fashion.

These studies raise the clear possibility that one could run appropriate tests on tissue or fluid samples remaining from a post mortem to establish the presence of elevated tryptase levels. If this were done, then it would amount to fairly conclusive evidence of an anaphylactic reaction as the cause of death in that case.  

It has been argued that menstruation and flushing could be linked to the incidence of anaphylaxis.
[“Anaphylaxis” T Prescott Atkinson and others vol 76 no 4 July 1992 – Index no 37 – Slater GE “Recurrent anaphylaxis in menstruating women”. See also “Incidence Aetiology and Management of AP presented to A & E Dept” QJ Med 1996 89 pp859ff].

Another case report indicated that where the autopsy was conducted after 14 hours, laryngeal oedema, lung congestion and the post mortem tryptase level in the blood was instrumental in confirming a diagnosis of acute anaphylaxis.
[ “Post mortem diagnosis of anaphylaxis by serum tryptase analysis – case report” Clinical Chemistry]

In this study, the authors compared the histamine (mast cell) and tryptase levels. 

Diagrams from: Martini, Anatomy and Physiology 5th edition, page 789.

Crusted Erythematous Post auricular Plaques

To give consideration to another matter which was not mentioned in the autopsy report in the Keogh case, we now have to explain a condition known as “crusted erythematous post auricular plaques”.

Crusted = hard dry formation on skin – scab

Erythematous = superficial inflammation of the skin in patches

Post auricular = behind the ear

Plaques = patch of eruption.

In plain English, this might be thought of as a localised inflammation which might be associated with swelling and redness, and which may have a scab or crusty surface, with some eruption, and found behind the ear(s).

This is the condition, which might be seen on the photograph of the deceased, which shows a redness and swelling behind the left ear. The condition might also be described as “pruritic lesions in the post auricular areas”

Pruritic = violent itching of the skin

Lesion = morbid change in functioning or texture of organ

Morbid = indicative of disease

A characteristic experience is that a person first notices blisters, which then become crusted. They may well be associated with intense itching. Such lesions may be found to be recurrent, but they are unlikely to be resolved completely. Whilst Dapsone therapy may lead to dramatic improvement, it is recommended that doses be individually titrated (adjusted) for each patient, to test the lowest levels at which the dapsone can be effective, as this will vary from patient to patient. [Archives of Dermatology volume 137(8) August 2001.1095-11].

The manufacturer of Dapsone has advised that the side effects of the drug are haemolysis and methaemoglobinaemia.

Haemolysis - the destruction of the red blood cells (erythrocytes) which results in anaemia.

Methaemoglobinaemia - the presence of methaemoglobin in the blood.

Methaemoglobin cannot bind molecular oxygen, and therefore cannot transport oxygen around the body. This causes the blood to have a more bluish colour and a patient suffering from this condition would be likely to show cyanosis – a blue colour. The blue of the blood vessels would be more pronounced, as we believe is the case in the photographs of the deceased in the Keogh case taken on the night of her death. This is most noticeable in the photographs of areas of the stomach and upper legs and thighs.

Drug analysis for those found on the premises

There is clear evidence of a number of drugs being present on the premises at the Keogh residence on the evening of the death in question. In June 1994, Michael Keogh made an inventory of property at the Cheney house, and this refers to “medications in the bathroom cabinet”. Given that there were a number of medications present in the house that evening one would have thought that testing of the deceased for the presence of such known drugs would have been mandatory.

However, Dr Byron Collins states in his report that the “negative results of the EMIT analysis are totally inadequate”. He states that “in a suspicious death, a wide ranging set of analytical procedures on various bodily fluids and organs such as blood, bile, urine, liver, stomach and contents must be performed.” There are no reports of this having been done in this case. This is particularly disturbing in the light of the facts of this particular case. There was much discussion during the trial as to whether the deceased could have become “light-headed” after standing in a warm bath. Something which could happen to any one of us.

However, if it were known that a well known side effect of medications which were present was “fainting and light-headedness”, then the failure to investigate this possibility would be more concerning. Again, we also find more references amongst these medications, to the possibility that an allergic reaction can occur. Given that this is a possibility for any “normal” user of those medications, it is clear that there is a heightened possibility of such a reaction where the user is already known to have a sensitivity to possible allergic reactions.

The following drugs are those which were recovered from the house.

Pyroxin

This is essentially vitamin B and is freely available without prescription. It is used for pre-menstrual tension and nausea. A container of this was found in the deceased’s handbag, behind the bedroom door, by the police.
[Constable Tyson’s statement 6 April 1994 p3 - “small white plastic bottle”- receipt no 389891 Payneham Police, also referred to in her notes].

Constable Tyson refers to the fact that she discussed this with somebody at the scene. The person to whom she spoke is not identified. This medication was mentioned in evidence at the trial, but little was made of it by either the prosecution or the defence. Given that there was much discussion at the trial of “vomitus material”, it is a clear possibility that Anna had been feeling the effects of nausea that evening and had resorted to the use of this medication.

Naprosyn

This is an anti-inflammatory. A container with this label was found on the top-shelf in the study and seized by the police on Wednesday 23 March 1994.
[McCue’s statement – 16 May 1994 p4 - received from Detective Man 10.09pm - plastic bottle with printed label NAPROSYN 500].

The following details are taken from the manufacturer’s advisory leaflet:

This is a non-steroid anti-inflammatory drug. NSAIDs are part of a larger family of drugs with similar effects. They are used to relieve pain, reduce inflammation, swelling, redness and soreness, which may occur in different types of arthritis, including rheumatoid arthritis or osteo-arthritis, and ankylosing spondylitis in muscle and bone injuries such as strains, sprains, lower back pain rheumatism and tendonitis, menstrual cramps.

Symptoms of an allergic reaction may include asthma, wheezing or shortness of breath, swelling of the face, lips or tongue, which may include difficulty in swallowing or breathing , hives (urticaria) oedema itching or skin rash or fainting. Symptoms which may occur include drowsiness, stomach upset, vomiting, nausea, dizziness or light-headedness. [Emphasis added]

Given that there is a specific warning being given by the manufacturer that a known side effect of this drug is an allergic reaction, which could produce drowsiness, dizziness, or light-headedness, one might have thought that it would have been important to undertake appropriate tests to determine if the deceased had this drug in her system. However, again there is no report that this was done. Furthermore, the warning given by the manufacturer specifically warns that:

Symptoms of an allergic reaction may include asthma, wheezing or shortness of breath, swelling of the face, lips or tongue, which may include difficulty in swallowing or breathing, hives (urticaria) oedema itching or skin rash, fainting. [Emphasis added]

The colour photographs taken at the scene that evening provide us with clear evidence that the deceased was suffering from “swelling of the face and lips” at least.
[See comments by Professor Maciej Henneberg in the Today Tonight programs for confirmation of this]

Importantly, for the purpose of our analysis, the manufacturer states that this can be accompanied by “shortness of breath” - “difficulty in swallowing or breathing” – “fainting” - the very matters which were being discussed at length during the proceedings at the trial.

However, the jury were clearly told that the deceased was “fit and healthy”. They were given no indication that the photographs indicated symptoms of an allergic reaction. 

That being the case, there would be no reason for them to suppose that the deceased might have become “light-headed” of have “fainted”, despite the fact that they were told that this could have happened to any ordinary person.

Perhaps if the jury had known that the deceased had a propensity to allergic reactions, then they might have evaluated the possibilities somewhat differently. If they had then known of the fact that the medication in the bathroom could have led to a swelling of the face, and difficulty in breathing and fainting, they might have thought this to be important also. Clearly the combination of a sensitivity to an allergic reaction, with medication known to have this particular propensity, could be considered to be the equivalent of a “smoking gun”. In this context, it is particularly disturbing that so little was made of the photographs, which show Anna to have had a swollen face, and clear indications of oedematous weals on her body.

It is also a matter of grave concern that the jury was not asked to consider these photographs in the light of the other photographs taken that evening which show that Anna’s face was “tidied up” [see comments of Professor Henneberg referred to].

In these circumstances it is even more problematic that we have neither colour photographs nor photographs of the whole body or face taken at post mortem.

Voltaren - Brufen - Indocid

Henry Keogh states that these drugs were available in the house, either through prescriptions, which had been used, or through “free samples” which had been obtained from a doctor who was a friend. These drugs are also used as anti-inflammatories. It is said that the deceased had access to these, and would use them if she felt the need to.

The deceased appears to have had an atopic history. This is a general term to cover allergic reactions, which include asthma and hayfever. It covers a range of oedema and extra-vascular activity, which is excess fluid outside the system of capillaries and veins. 

Plasma: colourless coagulable part of blood or lymph.

Serum: amber coloured liquid which separates from clot when blood coagulates

Additional Reading

“Anaphylactic Deaths” – Journal of Forensic Sciences Vol 33 (1988) pp1108-9.
Letter from Victor Weedn MD JD, University of Texas, Department of Pathology. States that death from anaphylaxis known about since 1972, and that tryptase as an indicator of anaphylaxis has been known since 1987.

“Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis” The New England Journal of Medicine Vol 316 (1987) pp1622-1626.
LB Schwartz, DD Metcalfe, JS Miller, H Earl, T Sullivan.
The plasma or serum tryptase level is a diagnostic correlate of mast cell related events. Tryptase is an enzyme, the presence of which can be a clinically useful marker of the release of mast cell granules. Substantial levels of tryptase have been found in the serum of patients undergoing clinically defined anaphylactic events.

“An unusual case of anaphylaxis” The American Journal of Forensic Medicine and Pathology 22(3) (2001) pp292-5.
A Bennett, KA Collins. Mould in pancake mix. A 19 year old male with a history of “multiple allergies” (pets, moulds, penicillin) ate mouldy pancake mix. He became short of breath, taken to a nearby clinic where he died. Autopsy found laryngeal oedema, hyperinflated lungs with mucous plugging. Microscopically, oedema and degranulating.

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