Anaphylaxis is a serious and potentially fatal allergic reaction that can progress rapidly. It typically causes more than one of the following: an itchy rash, throat closing due to swelling that can obstruct or stop breathing; severe tongue swelling that can also interfere with or stop breathing; shortness of breath, vomiting, lightheadedness, loss of consciousness, low blood pressure, and medical shock.
These symptoms typically start in minutes to hours and then increase very rapidly to life-threatening levels. Urgent medical treatment is required to prevent serious harm and death, even if the patient has used an epinephrine autoinjector or has taken other medications in response, and even if symptoms appear to be improving.
Common causes include allergies to insect bites and stings, allergies to foods—including nuts, peanuts, milk, fish, eggs; allergies to medications – including some antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs); or allergies to anaesthetics or latex. Other causes can include physical exercise, and cases may also occur in some people due to escalating reactions to simple throat irritation or may also occur without an obvious reason. The mast cell disease mastocytosis, along with the mast cell disorder mast cell activation syndrome are both capable of triggering anaphylaxis.
The mechanism involves the release of inflammatory mediators in a rapidly escalating cascade from certain types of white blood cells triggered by either immunologic or non-immunologic mechanisms. Diagnosis is based on the presenting symptoms and signs after exposure to a potential allergen or irritant.
The primary treatment of anaphylaxis is epinephrine injection into a muscle, intravenous fluids, then placing the person in a reclining position with feet elevated to help restore normal blood flow. Additional doses of epinephrine may be required. Other measures, such as antihistamines and steroids, are complementary. Carrying an epinephrine autoinjector, commonly called an "epipen", and identification regarding the condition is recommended in people with a history of anaphylaxis.
Immediately contacting ambulance / EMT services is strongly recommended, regardless of any on-site treatment. Getting to a doctor or hospital as soon as possible is important, even if the condition appears to be getting better.
Worldwide, 0.05–2% of the population is estimated to experience anaphylaxis at some point in life. Globally, as underreporting declined into the 2010s, the rate appeared to be increasing. It occurs most often in young people and females. About 99.7% of people hospitalized with anaphylaxis in the United States survive.
Etymology The word is derived from , and .
Signs and symptoms
Anaphylaxis typically presents many different symptoms over minutes or hours with an average onset of 5 to 30 minutes if exposure is intravenous and up to 2 hours if from eating food. 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.
Skin
Symptoms typically include generalized hives, itchiness, flushing, or swelling (angioedema) of the affected tissues. Those with 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 because of a lack of oxygen.
Respiratory Respiratory symptoms and signs that may be present include shortness of breath, wheezes, or stridor. The wheezing is typically caused by 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.
Cardiovascular While a fast heart rate caused by low blood pressure is more common, a Bezold–Jarisch reflex has been described in 10% of people, where a slow heart rate is associated with low blood pressure. A drop in blood pressure or shock (either distributive or cardiogenic) may cause the feeling of lightheadedness or loss of consciousness. In rare cases, very low blood pressure may be the only sign of anaphylaxis.
Coronary artery spasm may occur with subsequent myocardial infarction, dysrhythmia, or cardiac arrest. Those with underlying coronary disease are at greater risk of cardiac effects from anaphylaxis. The coronary spasm is related to the presence of histamine-releasing cells in the heart.
Other Gastrointestinal symptoms may include severe crampy abdominal pain and vomiting. There may be confusion, a loss of bladder control or pelvic pain similar to that of uterine cramps. Dilation of blood vessels around the brain may cause headaches. A feeling of anxiety or of "impending doom" has also been described.
Causes 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 and 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. Events caused by exercise are frequently associated with cofactors such as the ingestion of certain foods or taking an NSAID. Anaphylaxis caused by a combination of exercise and consumption of certain foods is known as food-dependent exercise-induced anaphylaxis (FDEIA). In aspirin-exacerbated respiratory disease (AERD), alcohol is a common trigger. 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." Six vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal) are recognized as a cause for anaphylaxis, and HPV may cause anaphylaxis as well.
Food and alcohol Many foods can trigger anaphylaxis; this may occur upon the first known ingestion. Common triggering foods vary around the world due to cultural cuisine. In Western cultures, ingestion of or exposure to peanuts, wheat, nuts, certain types of seafood like shellfish, milk, fruit and eggs are the most prevalent causes. Sesame is common in the Middle East, while rice and chickpeas are frequently encountered as sources of anaphylaxis in Asia. Severe cases are usually caused by ingesting the allergen, but some people experience a severe reaction upon contact. Children can outgrow their allergies. By age 16, 80% of children with anaphylaxis to milk or eggs and 20% who experience isolated anaphylaxis to peanuts can tolerate these foods. Any type of alcohol, even in small amounts, can trigger anaphylaxis in people with AERD.
Medication Any medication may potentially trigger anaphylaxis. The most common are β-lactam antibiotics (such as penicillin) followed by aspirin and NSAIDs. Other antibiotics are implicated less frequently. Anaphylactic reactions to NSAIDs are either agent specific or occur among those that are structurally similar, meaning that those who are allergic to one NSAID can typically tolerate a different one or a different group of NSAIDs. Other relatively common causes include chemotherapy, vaccines, protamine and herbal preparations. Some medications (vancomycin, morphine, x-ray contrast among others) cause anaphylaxis by directly triggering mast cell degranulation.
The frequency of a reaction to an agent partly depends on the frequency of its use and partly on its intrinsic properties. Anaphylaxis to penicillin or cephalosporins occurs only after it binds to proteins inside the body with some agents binding more easily than others. Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in fewer than one in every 50,000 courses of treatment. Anaphylaxis to aspirin and NSAIDs occurs in about one in every 50,000 persons. If someone reacts to penicillin, his or her risk of a reaction to cephalosporins is greater but still less than one in 1,000. The old radiocontrast agents caused reactions in 1% of cases, while the newer, lower osmolar agents cause reactions in 0.04% of cases. Avoidance of cephalosporins in those with penicillin allergy creates a significantly greater patient safety risk than the low probability of anaphylaxis.
Venom Venom from stinging or biting insects such as Hymenoptera (ants, bees, and wasps) or Triatominae (kissing bugs) may cause anaphylaxis in susceptible people. Previous reactions that are anything more than a local reaction around the site of the sting, are a risk factor for future anaphylaxis; however, half of the fatalities have had no previous systemic reaction.
Risk factors People with atopic diseases such as asthma, eczema, or allergic rhinitis are at high risk of anaphylaxis from food, latex, and radiocontrast agents but not from injectable medications or stings. One study in children found that 60% had a history of previous atopic diseases, and of children who die from anaphylaxis, more than 90% have asthma. Those with mastocytosis, mast cell activation syndrome (MCAS) or of a higher socioeconomic status are at increased risk.
Pathophysiology Anaphylaxis is a severe allergic reaction of rapid onset affecting many body systems. It is due to the release of inflammatory mediators and cytokines from mast cells and basophils, typically due to an immunologic reaction but sometimes with non-immunologic mechanisms.
Interleukin (IL)–4 and IL-13 are cytokines important in the initial generation of antibody and inflammatory cell responses to anaphylaxis.
Immunologic The vast majority of anaphylaxis is mediated by allergen-specific immunoglobulin E (IgE). In the immunologic mechanism, immunoglobulin E (IgE) binds to the antigen (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates FcεRI receptors on mast cells and basophils. This leads to the release of inflammatory mediators such as histamine. These mediators subsequently increase the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and compromise circulatory function.
Rarely, anaphylaxis may be triggered by immunoglobulin G (IgG) antibodies. Allergen-specific IgG is generally considered to be protective against allergic reactions (including anaphylaxis) because it competes with IgE for binding to the allergen (i.e., it is a blocking antibody) and its immune complexes (lattices of antigen and antibody, or in this case, allergen and IgG) inhibit IgE signaling.
Non-immunologic Non-immunologic mechanisms involve substances that directly cause the degranulation of mast cells and basophils without ligating the high-affinity IgE receptor. These include agents such as contrast medium, opioids, temperature (hot or cold), and vibration. Sulfites may cause reactions by both immunologic and non-immunologic mechanisms. This is a form of pseudoallergy and is commonly mediated by MRPRX2, a promiscuous receptor that interacts with many substances (especially drugs) to trigger mast cell degranulation without IgE.
Mixed type A form of anaphylaxis that has both IgE-dependent and non-IgE-dependent features has been observed as a consequence of some chemotherapy and monoclonal antibodies, manifesting alongside cytokine storm-like features.
Diagnosis Anaphylaxis is diagnosed on the basis of a person's signs and symptoms. When any one of the following three occurs within minutes or hours of exposure to an allergen there is a high likelihood of anaphylaxis: