What are Common Causes of Anaphylaxis?

Patient Presentation
A 4-year-old female came to clinic for her health maintenance appointment. She was known to have multiple food allergies and asthma and was managed by allergy specialists. Overall she was growing and developing well. The past medical history was positive for several episodes of rashes, facial edema with lip swelling, and wheezing that were provoked by various foods. She also had dust-mite allergy. She usually was treated with diphenhydramine and/or albuterol but once she started to have stridor and epinephrine was given and she was taken to the emergency room and hospitalized over night. The family history was positive for asthma and allergies.

The pertinent physical exam showed a fair-skinned smiling female with normal vital signs and growth parameters in the 10-25%. She had sensitive skin but otherwise had a normal examination.

The diagnosis of a healthy female with multiple allergies and one episode of anaphylaxis was made. The parents were very well versed in how to use her Epi-pen® and how to activate the emergency medical system. “We have several Epi-pens® but I think a couple of them are about to expire so we need some refills. This summer we are thinking about sending her to a daycare camp that will be at a farm. The allergist said it was okay as long as the daycare staff knows what to do if she seems to be having a reaction. We already checked and the ambulances are called using 911 since they are close to the city and the hospital is on that side of town too,” they stated. “It seems like a reasonable plan. I’d just make sure that her Epi-pen® is with them all the time like in a backpack and that the providers could really give her the epi if she needed it. You never know where they will be on the farm. You want her to be a normal kid but planning is important. Maybe if she doesn’t go this year, then another year when she is also even older and could possibly let people know if she seems to be having a problem. When you talk with them I’d ask them about the food the other kids will bring for lunch and snacks. You’ll need to do the same thing when she goes to kindergarten as well,” the pediatrician offered.

Anaphylaxis is a potentially life-threatening hypersensitivity reaction of the body. Usually anaphylaxis is IgE mediated but complement-mediated immune complex reactions or IgG mediated reactions can cause anaphylaxis. Usually mucous membranes or skin are involved, but it is a systemic disease process with at least 2 systems involved (respiratory is second most common followed by gastrointestinal system). The epidemiology is difficult to discern but the estimated incidence is about 50-112 episodes per 100,000 person-years and estimated prevalence is 0.3-5.1%. There is data supporting an increased incidence. Overall fatality is stable at about 0.63-0.75 per million adults in the US/year.

While it would seem to be easy to diagnose, anaphylaxis can be difficult for the patient and healthcare providers to recognize. Common signs and symptoms of anaphylaxis include:

  • Skin rash with or without pruritus, flushing, angioedema, conjunctival or perioral edema, urticaria
  • Respiratory – rhinitis or nasal congestion, dyspnea, wheezing, stridor, sensation of throat closing, choking, hypoxia
  • Gastrointestinal – nausea, emesis, abdominal pain, diarrhea
  • Cardiovascular – chest pain, diaphoresis, tachycardia or bradycardia, presyncope/syncope, hypotension, end-organ dysfunction
  • Central nervous system – confusion, headache, hypotonia, unconsciousness, seizure

Treatment with epinephrine right away and then transportation to a medical facility that can care for patients and appropriately monitor them is critical. Patients and families should be instructed that if epinephrine is given that the emergency medical system should be activated as the next step. Epinephrine may help but its duration of action is very short. Often it is needed to be given again. Health care providers can help patients by reviewing signs of anaphylaxis, and to make sure the family has enough epinephrine available (and it is not expired) as the patient may need multiple prescriptions to have on hand in multiple locations (ie home, school, relative or friends home, backpack, etc.). They should also be reminded how to use the epinephrine and to activate the medical system if they do.

Learning Point
The most common causes of anaphylaxis include:

  • Food – Overall, egg and milk are the most common food allergies. In children, egg, milk, soy, wheat and peanut allergies predominate. In adults, crustaceans, tree nuts, peanuts and fish predominate.
  • Drugs – beta-lactam antibiotics, nonsteroidal anti-inflammatory drugs
  • Exercise-induced anaphylaxis
  • Hymenoptera stings – honeybee, hornet, wasp, yellow jacket, fire ant
  • Latex – non-latex products are being used more often but still an important cause
  • Idiopathic

A recent review article by Dr. Katherine Anagnostou finishes by clearly stating, “Anaphylaxis is a severe life-threatening systemic reaction, which constitutes a clinical emergency. Prompt assessment and management are crucially important. Anaphylaxis is primarily a clinical diagnosis and health professionals should be appropriately trained in order to recognize and treat patients in a timely manner. Studies suggest that anaphylaxis is on the rise and that it is an under-recognized and under-reported medical diagnosis. Despite the increase in hospitalizations, fatalities from anaphylaxis are fortunately, rare. The commonest trigger in childhood is food. Severe, unstable asthma has been highlighted as a risk factor for severe anaphylaxis, therefore optimal control is key in order to manage risk. In addition, caregivers and patients are often reluctant to administer epinephrine due to uncertainty on whether this is required. Regular education of patients and families on how to identify anaphylactic episodes and respond appropriately is very important and should form part of the routine management.”

Questions for Further Discussion
1. Which proteins cause cow’s milk protein allergy? A review can be found here

2. What are risk factors for latex allergy? A review can be found here
3. What are common food allergy cross-reactivities? A review can be found here
Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Anaphylaxis and Allergy.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Anagnostou K. Anaphylaxis in Children: Epidemiology, Risk Factors and Management. Curr Pediatr Rev. 2018;14(3):180-186. doi:10.2174/1573396314666180507115115

Guo C, Greenberger PA. Idiopathic anaphylaxis. Allergy Asthma Proc. 2019;40(6):457-461. doi:10.2500/aap.2019.40.4271

Poowuttikul P, Seth D. Anaphylaxis in Children and Adolescents. Pediatr Clin North Am. 2019;66(5):995-1005. doi:10.1016/j.pcl.2019.06.005

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa