Here's a short video which displays how anaphylaxis can be a silent killer.







To start off our first post on this blog,

let's look at this real story taken from http://www.allergicliving.com/features.asp?copy_id=103


Teen Tragedies
The shocking deaths of two teens provide clues to what goes wrong in
fatal reactions.

By Gwen Smith
and Karen Eck


When news surfaced that 15-year-old Christina Desforges of Saguenay, Quebec, had died of what appeared to be an anaphylactic reaction to a kiss from a boyfriend who had eaten a peanut butter sandwich, the story travelled from Canada to Mexico to South Africa and on to Europe.


The reason for the media interest was simple: it seemed incredible that death could come from the tiny amount of peanut encountered in a kiss. Not only that, but the young man had eaten his sandwich about nine hours before the kissing started.



The investigation into Christina’s death in November, 2005 is raising questions about whether anaphylaxis and the kiss were to blame – or, at least, solely to blame.



In early March, Coroner Michel Miron told the Quebec media that Christina did not die from peanut exposure through a kiss, but added that he had further tests to
complete. At press time, Miron was still finalizing his report and was considering asthma as the likely main cause of death. However, a leading Canadian allergy expert has told Allergic Living that it may be difficult to entirely rule out anaphylaxis, the severe food allergic reaction, because the condition is inter-related with asthma.



But whatever the final pathology report concludes, what is certain is that Christina was having great trouble breathing at her boyfriend’s home in the early hours of November 21.



She was asthmatic and allergic to peanut. If anaphylaxis or asthma or both were the cause of her respiratory distress, Allergic Living has learned this as well: contrary to the news reports, Christina did not get epinephrine promptly. “It really was not ‘immediately’,” confirmed Dr. Nina Verreault, the Saguenay allergist working with the coroner.



“It was more like ‘late’.”



This is not the only recent allergy-related teenage tragedy. A month after Christina died, Chantelle Yambao of Edmonton, who was severely allergic to nuts and peanuts, ate a store-bought Nanaimo square and began to feel shortness of breath.



Thinking she was having an asthma attack, the 13-year-old used her bronchodilator (or puffer). Hours passed on December 23, 2005, before she let her mother know of her breathing trouble. Then Chantelle collapsed. Her parents phoned 911, but the teen was well into a serious reaction. She lost consciousness and was put on life support in hospital. She died a few days later.




Isn't that scary?

Due to allergies, these two innocent lives were taken away just like that.


So now, Let's move on to know more in depth about anaphylaxis in general and also its clinical features!



INTERESTING FACT: About 1% to 2% of Canadians are at risk of an anaphylactic reaction!

Woah! My first time encountering such a word called anaphylaxis. The first thought that came to my mind : Is anaphylaxis a symptom or a serious disease? After looking up the web I found out that it was actually a life threatening allergic reaction. The term comes from the Greek words ανα ana (against) and φύλαξις phylaxis (protection). Medical terms sure knows how to come up with this word! :)

So what does Anaphylaxis actually mean?
Here's a story of how it came about, which dates back about 100 years ago.

The story begins on a cruise aboard Prince Albert I of Monaco's yacht. The Prince had invited two Parisian scientists to perform studies on the toxin produced by the tentacles of a local jellyfish, the Portuguese Man of War. Charles Richet and Paul Portier were able to isolate the toxin and tried to vaccinate dogs in the hope of obtaining protection, or "prophylaxis," against the toxin. They were horrified to find that subsequent very small doses of the toxin unexpectedly resulted in a new dramatic illness that involved the rapid onset of breathing difficulty and resulted in death within 30 minutes. Richet and Portier termed this "anaphylaxis" or "against protection." They rightly concluded that the immune system first becomes sensitized to the allergen over several weeks and upon re-exposure to the same allergen may result in a severe reaction.


So, Anaphylaxis means a general allergic reaction which is considered an acute, severe reaction, often with hypotension, resulting from the release of bioactive mediators from mast cells which are responsible for the clinical features. They can be categorised as mild, moderate or severe.




Clinical diagnosis of anaphylaxis involves the recognition of one or both of the two severe features of airway compromise (laryngeal oedema and/or asthma)
and hypotension (collapse, loss of consciousness, fainting).

For example, urticaria and angio-oedema, in the absence of laryngeal oedema or airway involvement, is not anaphylaxis.


General Features of anaphylaxis also includes:
· Erythema
· Angio­oedema
· Laryngeal oedema
· Asthma
· Itching of palate or external auditory meatus
· Nausea, vomiting, abdominal pain
· Sense of impending doom
· Fainting, lightheadedness
· Collapse
· Loss of consciousness




People with asthma, seasonal allergies, or eczema are at a higher risk of anaphylaxis. Before age 16, anaphylaxis is more common in boys than in girls. After age 30, it is more common in women than in men. Race and geographic location do not affect the risk of anaphylaxis.


CITATION:

Anaphylaxis symptoms,diagnosis, treatment and causes- wrongdiagnosis.com(2010). Retrived 6 Feb 2010 from: http://www.wrongdiagnosis.com/a/anaphylaxis/intro.htm


Anaphylaxis-Causes, symptoms,treatment, diagnosis-common factsheets, Body&Health.(2010) Retrived 6 Feb 2010 from:http://bodyandhealth.canada.com/condition_info_details.asp?disease_id=319


Anaphylaxsis symptoms and diagnosis,F Estelle R Simons(2010) Retrived 6 Feb 2010 from : http://www.uptodate.com/patients/content/topic.do?topicKey=~u55pia.nJGQ/Gs


Anaphylaxis(Severe Allergic Reaction)Symptoms, causes, treatment,and prevention. Jerry R. Balentine, Melissa Conrad Stöppler(2010) Retrived 6 Feb 2010 from: http://www.medicinenet.com/anaphylaxis/article.htm

When a person with an anaphylactic allergy is exposed to an allergen (something they are allergic to), their immune system goes into overdrive.

The substances it produces, such as histamine, are intended to protect the body from a foreign invader. But they go much too far, causing the throat to swell up and the blood vessels to leak fluid.

This leads to the symptoms of anaphylaxis and can be life-threatening.

When an allergen is inserted systemically, cardiovascular problems, especially hypotension and shock will have a high possibility to occur.

This is due to the large boluses which are given intravenously during the induction of anaesthesia. When eating, the food which absorbed will cause lip, facial and Laryngeal oedema.

Respiratory difficulty will therefore be in the majority.



References:

Anaphylaxis symptoms,diagnosis, treatment and causes- wrongdiagnosis.com(2010). Retrived 6 Feb 2010 from: http://www.wrongdiagnosis.com/a/anaphylaxis/intro.htm


Anaphylaxis-Causes, symptoms,treatment, diagnosis-Condition factsheets, Body&Health.(2010) Retrived 6 Feb 2010 from:http://bodyandhealth.canada.com/condition_info_details.asp?disease_id=319


Anaphylaxsis symptoms and diagnosis,F Estelle R Simons(2010) Retrived 6 Feb 2010 from : http://www.uptodate.com/patients/content/topic.do?topicKey=~u55pia.nJGQ/Gs

There are 2 Major Groups:

IgE mediated: This form is the true anaphylaxis that requires an initial sensitizing exposure, the coating of mast cells and basophils
(cells in the blood and tissue that secrete the substances that cause allergic reactions, known as mediators)
by IgE, and the explosive release of chemical mediators upon re-exposure.

Non-IgE mediated: These reactions, the so called "anaphylactoid" reactions, are similar to those of true anaphylaxis, but do not require an IgE immune reaction.

They are usually caused by the direct stimulation of the mast cells and basophils. The same mediators as occur with true anaphylaxis are released and the same effects are produced.

This reaction can happen, and often does, on initial as well as subsequent exposures, since no sensitization is required.




This can be initiated in response to an allergen!
And these include:

Drug allergies
Food allergies
Insect bites/stings (E.g: Bee sting)

In the next post, we will be discussing more about these allergies!


Citation:

Common Agents involved in Anaphylaxis and their mechanisms
(n.d.) Anaphylaxis. Retrieved from 6th February 2010.From,
http://www.allergysa.org/anaphyl.htm

Survive Outdoors.(2000). Pathophysiology of Bee Stings. Retrieved from 6th February 2010. From,
http://www.surviveoutdoors.com/reference/beeswasps/index.asp

Medical News Today.(2010).Common Food Allergies. Fetrieved from 6th February,2010. From,
http://www.medicalnewstoday.com/articles/8624.php

Medicine Net.com We bring Doctor’s knowledge to you.(n.d.) Anaphylaxis (cont.). Retrieved from 6th feb 2010.From
http://www.medicinenet.com/anaphylaxis/page5.htm
Food Reactions.(2005) Food Allergy.Retrived from 6th February 2010.From
http://www.foodreactions.org/allergy/

MedlinePlus. (n.d.) Histocompatibility antigen test.Retrieved from 6th feb 2010. from,
http://www.nlm.nih.gov/medlineplus/ency/article/003550.htm

How it works?

Anaphylaxis occurs when a person is reexposed to a specific antigen that cross-links antigen- specific IgE molecules, which are bound to mast cells and basophils.
This leads to activation and degranulation of mast cells and basophils. Preformed mediators, such as histamine and tryptase, within the mast cell and basophil are released in degranulation. The metabolism of arachidonic acid in the cell membrane produces other mediators, such as prostaglandins and leukotrienes.
These mediators act on receptors to induce mucus production, pruritus, vascular permeability, smooth-muscle constriction, and other symptoms of anaphylaxis (Rusznak, 2002). Rapid release of large quantities of mediators systemically will cause capillary leakage and mucosal edema, resulting in shock and asphyxia (Ewan, 1998).


Immunological Mechanism of Anaphylaxis:
(1) Antigen-presenting cell internalizes antigen. (2) The APC processes the internalized antigen. (3) The APC presents the processed peptide to CD4+ T lymphocytes via MHC II. (4) After the peptide is presented, the T cell differentiates into TH2 lymphocytes and produces IL-4, IL-5, IL-9, and IL-13. (5) IL-4 and IL-13 cause B cell immunoglobulin isotype switching to IgE. (6) The circulating IgE binds to the IgE receptors on mast cells. (7) Antigen similar to the original antigen cross-links the mast cell surface-bound IgE, resulting in cellular degranulation. Degranulation releases histamine, tryptase, and other mediators that produce the symptoms of anaphylaxis (Anaesthesia UK, 2005).

Figure 1: Overview of Immunological Mechanism of Anaphylaxis. This figure illustrates each step of the immunological mechanism for anaphylaxis. Figure taken from Anaesthesia UK( 2004), permission pending.

Now as we discuss in the following post, there are 3 different kinds of allergies that causes Anaphylaxis and these includes,




1. Drug Allergy:

Some drugs (polymyxin, morphine, x-ray dye, and others) may cause an anaphylactic-like reaction (anaphylactoid reaction) when people are first exposed to them. This is usually due to a toxic reaction, rather than the immune system response that occurs with "true" anaphylaxis.
The symptoms, risk for complications without treatment, and treatment are the same, however, for both types of reactions. These are the common antibiotics that are associated with anaphylaxis:

Penicillin
Cephalosporins
Tetracycline
Nitrofurantoin
Vancomycin
Chloramphenicol
Bacitracin
Neomycin
Kanamycin
Amphoterin B

The immune system protects the body from potentially harmful substances by recognizing and responding to antigens. Antigens are molecules (usually proteins) on the surface of cells, viruses, fungi, or bacteria. The immune system recognizes and destroys substances that contain these antigens.
Even your own body cells have proteins that are antigens. These include a group of antigens called HLA antigens. Your immune system learns to see these antigens as normal and does not usually react against them.
A histocompatibility antigen blood test looks at proteins called human leukocyte antigens (HLAs), which are found on the surface of nearly every cell in the human body. HLAs are found in large amounts on the surface of white blood cells. They help the immune system tell the difference between body tissue and foreign substances.


2. Food Allergy:

Examples of food allergy:

• milk (caseins and the whey protein b –lactoglobulin)



• eggs (egg white proteins ovomucoid, ovalbumin, and ovotransferrin



• peanuts and tree nuts (proteins used by the seed)



• nuts from trees (including Brazil nuts, hazelnuts, almonds and walnuts)
  
  
• fish (flesh proteins called parvalbumins)



• shellfish eg.including mussels, crab and shrimps (flesh and are part of the muscle protein system, whilst shrimps, allergens have also been found in the shells



• soya ( proteins)



• wheat ( wheat gluten)
  

So what is a Food Allergy?!


Our bodies are protected from infections by our immune system. We produce a type of proteins, called antibodies, which recognise the germs causing an infection. There are a number of different sorts of antibodies, and the one which causes an allergic reaction is called IgE.

Free IgE antibodies (green) cleave to food antigens (red stars) e.g. milk proteins. This cleavage forces the IgE ab to coat the mast cell signalling a danger. The mast cell releases granules of chemical toxins. These granules burst and release these potent chemicals which bring on the allergy attack.

The IgE acts like a tag, sticking to molecules in food or pollen called allergens. When someone who has an allergy eats a problem food the IgE attaches to the allergens, setting off an allergic reaction. One of the common effects that IgE triggers is the release of histamine, which causes the changes we see in our bodies as symptoms, like nettle rash or wheezing.


Allergens are usually proteins, and there are generally several kinds of allergen in each food. It is not fully understood why some foods can cause allergies and others do not, but a theory is that it is probably that some proteins in foods mimic very closely proteins present in viruses and bacteria.


Hence, in some persons, usually this is genetically predisposed, as our immune system is not able to distinguish the food protein from the virus or bacteria one, hence it attacks.



3. Insect Stings:

Examples:

Honeybees
Yellow jackets
Hornets
Wasps
Fire Ants


I will talk about bee stings since this is the most common stings among all.


Bees stings























Do you know that the venom of bees, wasps and fire ants contains phospholipase A2, hyaluronidase, apamin, meliltin, and kinins.




Our body quickly overreacts with histamine production. Histamine is found in higher concentrations in skin, lungs, and stomach mucosa. The release of histamine from the mast cells is usually triggered by skin disruption, i.e. bee sting. Histamine is a potent arterial dilator. Individuals therefore can become hypotensive (lowering of blood pressure) and may pass out.





Histamine can cause inflammation directly as well as indirectly. Upon release of histamine by an antigen activated mast cell, permeability of vessels near the site is increased. Thus, blood fluids (including leukocytes, which participate in immune responses) enter the area causing swelling. This is accomplished due to histamine’s ability to induce phosphorylation of an intercellular adhesion protein (called (VE)-cadherin) found on vascular endothelial cells (Andriopoulou et al 1999). That is why histamine is known as being vasoactive. Gaps between the cells in vascular tissue are created by this phosphorylation, allowing blood fluids to seep out into extracellular space. Indirectly, histamine contributes to inflammation by affecting the functions of other leukocytes in the area. It has been suggested by Marone et al that histamine release triggers the release of cytokines and inflammatory mediator by some neighboring leukocytes (1999). These chemicals in turn increases the inflammatory response.





Interesting Facts about bee stings:
Average adult can withstand approximately 1000 stings
500 stings can kill a child.
Anaphylaxis and death can occur from one sting if the individual is highly allergic.
Therefore do not worry if you get stung by a bee unless you are allergic to it!!!













Common Agents involved in Anaphylaxis and their mechanisms
(n.d.) Anaphylaxis. Retrieved from 6th February 2010.From,
http://www.allergysa.org/anaphyl.htm

Survive Outdoors.(2000). Pathophysiology of Bee Stings. Retrieved from 6th February 2010. From,
http://www.surviveoutdoors.com/reference/beeswasps/index.asp

Medical News Today.(2010).Common Food Allergies. Fetrieved from 6th February,2010. From,
http://www.medicalnewstoday.com/articles/8624.php

Medicine Net.com We bring Doctor’s knowledge to you.(n.d.) Anaphylaxis (cont.). Retrieved from 6th feb 2010.From
http://www.medicinenet.com/anaphylaxis/page5.htm
Food Reactions.(2005) Food Allergy.Retrived from 6th February 2010.From
http://www.foodreactions.org/allergy/

MedlinePlus. (n.d.) Histocompatibility antigen test.Retrieved from 6th feb 2010. from,
http://www.nlm.nih.gov/medlineplus/ency/article/003550.htm


Anaphylaxis, Davidson collage.(2010) Retrived 5th Feb 2010 from: http://www.bio.davidson.edu/courses/immunology/Students/spring2006/Witcher/Anaphylaxis.html

The most effective drugs for anaphylaxis and should be given to patients with respiratory difficulty or hypotension is called the Adrenaline (epinephrine).

However, the treatment will not work if the adrenaline is delayed.

• In the management of anaphylaxis, it usually involves treatments using mainly epinephrine and histamine as a supplementary treatment. Treatment also involves post therapy which ensures that symptoms do not relapse.
  
  Dosage of epinephrine for adults in treatment is 0.3–0.5 mL of a 1:1000 dilution, while dosage for children is 0.01 mL/kg, up to a maximum 0.3 mL of a 1:1000 dilution.

• Epinephrine is injected in 5-15 minutes intervals until the symptoms of hyperandrealism show up on the patient. There are also intravenous epinephrine (1:10 000 dilution) but should only be used in extreme cases because of the potential to trigger tachrrhythmias.During treatment, the patient’s airways must be sufficiently opened and maintained while having oxygen tanks on standby for patients with anaphylactic reactions.
  
  
  
• Supplemtary treatment includes the use of H₁ and H₂ antihistamines like diphenhydramine, in which 25-50 mg is injected and ranitidine is taken orally 150mg each time or 50mg is injected.
  It is recommended to use these 2 treatments at the same time as H₁ and H₂ blockage is more effective than using H₁ blockage alone.

• Hypotensive patients should receive intravenous fluid support with crystalloid or colloid, and severe cases may require vasopressor agents such as dopamine or high-dilution epinephrine (1:10 000).

• Individuals who use ß-blockers (and possibly angiotensin-converting-enzyme inhibitors, although the evidence is incomplete) may not respond completely to epinephrine, in which case glucagon should be administered at a dose of 5–15 µg/min intravenously. Glucagon has inotropic, chronotropic and vasoactive effects that are independent of ß-receptors, and it also causes endogenous catecholamine release.

• The person may receive antihistamines, such as diphenhydramine, and corticosteroids, such as prednisone, to further reduce symptoms (after lifesaving measures and epinephrine are administered).

• Lastly, these patients require post-treatment observation to prevent relapse of anaphylaxis. Monitored settings of 24 hours are often optimal for most cases. Patients are often only discharged when the doctors can confirm he/she is not any life threatening situation.
  
  
  
• Prevention

Avoid known allergens. Any person experiencing an allergic reaction should be monitored, although monitoring may be done at home in mild cases.

Occasionally, people who have a history of drug allergies may safely be given the medication they are allergic to after being pretreated with corticosteroids (prednisone) and antihistamines (diphenhydramine).

People who have a history of allergy to insect bites/stings should carry (and use) an emergency kit containing injectable epinephrine and chewable antihistamine. They should also wear a MedicAlert or similar bracelet or necklace stating their allergy.

References:

Diagnosis and Management of anaphylaxsis - ellis and day 169(4):307 --canadian medical association ,Anne K. Ellis and James H. Day,(2003). retrived 6th Feb 2010 from:http://www.cmaj.ca/cgi/content/full/169/4/307#T123#T123