The immune system protects us from external invasion by pathogens (bacteria, virus, fungus, parasites) and internal invasion, such as when our own cells reproduce abnormally to form tumors and cancers.

The first step is to recognize these threats as foreign and potentially dangerous. There are surface molecules on these pathogens and abnormal cells that the immune system identifies as foreign (an antigen). Antigens trigger the immune system. Non-living substances can also be antigens and produce an immune response: toxins, chemicals, drugs, and foreign objects that find their way into normal tissue (splinters, glass, lead, etc).

The antigen stimulates an attack response that occurs on several fronts: antibodies attach directly to the antigen and can neutralize the offenders; immune cells that can destroy the invaders appear on scene; defensive chemicals are released to enhance destruction; and cellular vacuum cleaners, or macrophages, appear to help clean up the mess. (Get more information about the immune system at http://www3.niaid.nih.gov/topics/immuneSystem/default.htm).

Unfortunately, the immune system can make mistakes and recognize normal tissue as foreign, such as in rheumatoid arthritis, where the immune system attacks normal cartilage. Problems also arise when non-threatening antigens make their way into the body and sensitize the immune system to respond to any subsequent exposures. Every year millions of us suffer itchy, teary eyes and a leaky nose as the pollen count increases. This unproductive response is called an allergy, or allergic reaction, and can range from minor discomfort to a fatal event. The antigen has become an allergen.

A Little History
In 1902, Drs. Portier and Richet from France extracted sea anemone toxin and attempted to desensitize dogs (decrease their immune response) to the effects of the toxin. By injecting small amounts, the toxin produced a mild reaction (itching, mild dyspnea), which would hopefully diminish the response to a larger injection later.

However, when the larger dose was injected several weeks later, the dogs exhibited severe symptoms of vomiting, bloody diarrhea, unconsciousness and rapid death. The animals had become highly sensitive (excessive immune response) to the toxin and died. To describe their observations, these researchers used the Greek word phylaxis, meaning immunity and protection, to create a term to describe the anti-protective effect of the earlier sensitization: anaphylaxis. Subsequent researchers confirmed their findings.

Definition
In 2005, the National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network held a second symposium on anaphylaxis, producing the following definition:

Overview
The best guess is that anaphylaxis affects 1 to 15 percent of the US population. The difficulty in identifying a more accurate count of anaphylaxis cases comes from the unknown number of unreported or unrecognized cases. Unreported cases could include the patient with a history of anaphylaxis who uses an epinephrine auto-injector, but does not notify their physician or end up in the local emergency department. Unrecognized cases could include the patient who presents with dyspnea, wheezing and hypoxia due to anaphylaxis, but is diagnosed with asthma or a cardiac condition. It can be difficult to sort out.

In evaluating your patient, it may be useful to remember that food allergy, insect stings, medications and latex account for the majority of anaphylaxis cases. And the risk factors for anaphylaxis include a previous episode, history of asthma and unrecognized exposure to known triggers (like having a latex allergy and being surprised on contact with one of the many household products that contain latex).

Death by anaphylaxis is caused by shock and/or respiratory arrest. Contributing factors include unrecognized anaphylaxis and/or delayed treatment. Although fatal anaphylaxis is reported to be less than 1 percent, it is under-reported due to the difficulty in diagnosing anaphylaxis after death has occurred.

Treatment
The same group of experts noted above identified epinephrine as the treatment of choice for anaphylaxis: 0.01 mg/kg, maximum dose 0.5 mg, given intramuscular, with repeated dosing every five to 15 minutes as needed to control symptoms and maintain adequate blood pressure. They also noted the five-minute interval can be shortened depending on severity of symptoms. And for circulatory collapse, intravenous epinephrine is an option. The intravenous dose depends on severity; titrate to effective perfusion pressure (systolic BP 90-100 mmHg).

Although the potential for an adverse reaction to epinephrine is low when used for anaphylaxis, it is important to remember that epinephrine is a sympathomimetic. That means it produces the same effects as your own sympathetic nervous system when called upon for a 'fight or flight' response: vasoconstriction, increased heart rate, increased heart contractility, increased respiratory rate and bronchodilation. All of these actions are good for the patient with anaphylaxis, but potentially harmful in the absence of anaphylaxis.

Of course, treatment includes simultaneous support of airway, breathing and circulation. Albuterol can be administered for wheezing from bronchospasm, but is not a substitute for epinephrine in anaphylaxis. For declining blood pressure, place the patient supine and administer intravenous fluids (sometimes lots of fluid) along with the epinephrine.
Anaphylaxis can cause life-threatening dilatation of the blood vessels. This produces a decrease or absent blood flow to the right ventricle. And if there is a decrease to the right ventricle, then there is a decrease to the left ventricle, resulting in decreased or absent blood pressure. 'Empty ventricle syndrome' describes the extreme condition of a beating but empty heart, which quickly becomes a non-beating empty heart if not treated rapidly.

Summary
Surviving anaphylaxis depends on rapid recognition and early treatment with epinephrine. That's often easier said than done. However, you can improve your patient’s chances that this will occur by maintaining your ability to recall the various clinical presentations and risk factors for anaphylaxis and keeping your epinephrine handy.

References

• U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Cancer Institute. Understanding the Immune System, How it Works. NIH Publication No. 03-5423, September 2003.
• May CD. The ancestry of allergy: Being an account of the original experimental induction of hypersensitivity recognizing the contribution of Paul Portier. J. Allergy Clin. Immunol. 1985; 75(4):485-495
• Sampson HA, Munoz-Frulong A, Campbell RL, et al. Second Symposium of the Definition and Management of Anaphylaxis: Summary Report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium. Ann Emerg Med. 2006;47:373-380.
• Neugat AI, Ghatak AT, Miller RL. Anaphylaxis in the United States, An Investigation Into Its Epidemiology. Arch Intern Med; 2001;161:15-21.
• Pumphrey RSH. Anaphylaxis: Can We Tell Who is at Risk of a Fatal Reaction? Curr Opin Allergy Clin Immunol. 2004;4(4):285-290.
• Kumar A, Teuber SS, Gershwin TM. Why do people die of anaphylaxis? — A clinical review. Arch Intern Med.2001;161:15-21.
• McLean-Tooke APC, Bethune CA, Fay AC, Spickett GP. Adrenaline in the treatment of anaphylaxis: what is the evidence? BMJ. 2003; 327:1332-1335.