Anaphylaxis

Definition

Definition of Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including an itchy rash, throat swelling, and low blood pressure. Common causes include insect bites, foods, and medications.

On a pathophysiologic level, anaphylaxis is due to the release of mediators from certain types of white blood cells triggered either by immunologic or non-immunologic mechanisms. It is diagnosed based on the presenting symptoms and signs. The primary treatment is injection of epinephrine, with other measures being complementary.

Symptoms

Symptoms of Anaphylaxis
Anaphylaxis typically presents with many different symptoms over minutes or hours with an average onset of 5 to 30 minutes if exposure is intravenous and 2 hours for foods. The most common areas affected include: skin (80-90%), respiratory (70%), gastrointestinal (30-45%), heart and vasculature (10-45%), and central nervous system (10-15%) with usually two or more being involved.

1. Skin: Symptoms typically include generalized hives, itchiness, flushing or swelling of the lips. Those with swelling or angioedema may describe a burning sensation of the skin rather than itchiness. Swelling of the tongue or throat occurs in up to about 20% of cases. Other features may include a runny nose and swelling of the conjunctiva. The skin may also be blue tinged due to a lack of oxygen.
2. Respiratory: Respiratory symptoms and signs that may be present, including shortness of breath, wheezes or stridor. The wheezing is typically due to spasms of the bronchial muscles while stridor is related to upper airway obstruction secondary to swelling. Hoarseness, pain with swallowing, or a cough may also occur.
3. Cardiac: Coronary artery spasm may occur with subsequent myocardial infarction, dysrhythmia, or cardiac arrest. Those with underlying coronary disease are at greater risk of cardiac affects from anaphylaxis. The coronary spasm is related to the presence of histamine-releasing cells in the heart. While a fast heart rate due to low blood pressure is more common, a Bezold–Jarisch reflex has been described in 10% of cases, where a slow heart rate is associated with low blood pressure. A drop in blood pressure or shock (either distributive or cardiogenic) may result in the feeling of lightheadedness or loss of consciousness. Rarely very low blood pressure may be the only sign of anaphylaxis.

Causes

Causes of Anaphylaxis
Anaphylaxis can occur in response to almost any foreign substance. Common triggers include venom from insect bites or stings, foods, and medication. Foods are the most common trigger in children and young adults while medications and insect bites and stings are more common in older adults. Less common causes include: physical factors, biological agents such as semen, latex, hormonal changes, food additives such as monosodium glutamate and food colors, and topical medications. Physical factors such as exercise (known as exercise-induced anaphylaxis) or temperature (either hot or cold) may also act as triggers through their direct effects on mast cells. Exercise induced events are frequently associated with the ingestion of certain foods. During anesthesia, neuromuscular blocking agents, antibiotics, and latex are the most common causes. The cause remains unknown in 32-50% of cases, referred to as "idiopathic anaphylaxis".

Diagnosis

Diagnosis of Anaphylaxis
Anaphylaxis is diagnosed based on clinical criteria. When any one of the following three occurs within minutes/hours of exposure to an allergen there is a high likelihood of anaphylaxis:

1. Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure
2. Two or more of the following symptoms:-

• Involvement of the skin or mucosa
• Respiratory difficulties
• Low blood pressure
• Gastrointestinal symptoms

3. Low blood pressure after exposure to a known allergen

Treatment

Treatment of Anaphylaxis
Anaphylaxis is a medical emergency that may require resuscitation measures such as airway management, supplemental oxygen, large volumes of intravenous fluids, and close monitoring. Administration of epinephrine is the treatment of choice with antihistamines and steroids often used as adjuncts. A period of in hospital observation for between 2 and 24 hours is recommended for people once they have returned to normal due to concerns of biphasic anaphylaxis.

1. Epinephrine: Epinephrine (adrenaline) is the primary treatment for anaphylaxis with no absolute contraindication to its use. It is recommended that an epinephrine solution be given intramuscularly into the mid anterolaterial thigh as soon as the diagnosis is suspected. The injection may be repeated every 5 to 15 minutes if there is insufficient response. A second dose is needed in 16 to 35% of episodes with more than two doses rarely required. The intramuscular route is preferred over subcutaneous administration because the latter may have delayed absorption. Minor adverse effects from epinephrine include tremors, anxiety, headaches, and palpitations. People on B-blockers may be resistant to the effects of epinephrine. In this situation if epinephrine is not effective intravenous glucagon can be administered which has a mechanism of action independent of ß-receptors. If necessary, it can also be given intravenously using a dilute epinephrine solution. Intravenous epinephrine however has been associated both with dysrhythmia and myocardial infarction. Epinephrine autoinjector used for self-administration typically in two doses, one for adults or children who weight more than 25 kg and one for children who weight 10 to 25 kg.
2. Adjuncts: Antihistamines (both H1 and H2), while commonly used and assumed effective based on theoretical reasoning, are poorly supported by evidence. A 2007 Cochrane review did not find any good-quality studies upon which to base recommendations and they are not believed to have an effect on airway edema or spasm. Corticosteroids are unlikely to make a difference in the current episode of anaphylaxis, but may be used in the hope of decreasing the risk of biphasic anaphylaxis. Their prophylactic effectiveness in these situations is uncertain. Nebulized salbutamol may be effective for bronchospasm that does not resolve with epinephrine. Methylene blue has been used in those not responsive to other measures due to its presumed effect of relaxing smooth muscle.
3. Preparedness: People prone to anaphylaxis are advised to have an "allergy action plan", and parents are advised to inform schools of their children's allergies and what to do in case of an anaphylactic emergency. The action plan usually includes use of epinephrine auto-injectors, the recommendation to wear a medical alert bracelet, and counseling on avoidance of triggers. Immunotherapy is available for certain triggers to prevent future episodes of anaphylaxis. A multi-year course of subcutaneous desensitization has been found effective against stinging insects, while oral desensitization is effective for many foods.

Prognosis

Prognosis of Anaphylaxis
In those in whom the cause is known and prompt treatment is available, the prognosis is good. Even if the cause is unknown, if appropriate preventative medication is available, the prognosis is generally good. If death occurs, it is usually due to either respiratory (typically asphyxia) or cardiovascular causes (shock), with 0.7–20% of cases resulting in death. There have been cases of death occurring with minutes. Outcomes in those with exercise-induced anaphylaxis are typically good, with fewer and less severe episodes as people get older.

Prevention

Prevention of Anaphylaxis
Avoidance of the trigger of anaphylaxis is recommended. In cases where this may not be possible, desensitization may be an option. Immunotherapy with Hymenoptera venoms is effective at desensitizing 80–90% of adults and 98% of children against allergies to bees, wasps, hornets, yellowjackets, and fire ants. Oral immunotherapy may be effective at desensitizing some people to certain food including milk, eggs, nuts and peanuts; however adverse effects are common. Desensitization is also possible for many medications, however it is advised that most people simply avoid the agent in question. In those who react to latex it may be important to avoid cross-reactive foods such as avocados, bananas, and potatoes among others.