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Phenotype Submission - Anaphylaxis

Clinical Description

Authoritative source:

Related OHDSI work: Phenotype Phebruary Day 24 - Anaphylaxis

Overview: Acute potentially life-threatening multisystem syndrome due to mast cell mediator release most often via IgE. For diagnostic criteria see Sampson criteria

Presentation: Anaphylaxis is highly likely when any ONE of the following three criteria is fulfilled (sampson criteria):
Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula) AND


  1. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, hypoxemia)
  2. Reduced BP* or associated symptoms of end-organ dysfunction (e.g., hypotonia, collapse, syncope, incontinence)

TWO OR MORE OF THE FOLLOWING that occur rapidly after exposure to a LIKELY allergen for that patient (minutes to several hours):

  1. Involvement of the skin mucosal tissue (e.g., generalized hives, itch-flush, swollen lips-tongue-uvula)
  2. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, hypoxemia)
  3. Reduced BP* or associated symptoms (e.g., hypotonia, collapse, syncope, incontinence)
  4. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)

Reduced BP* after exposure to a KNOWN allergen for that patient (minutes to several hours):

  1. Infants and children - Low systolic BP (age-specific for pediatrics) or greater than 30% decrease in systolic BP
  2. Adults - Systolic BP of less than 90 mmHg or greater than 30% decrease from that person’s baseline

Assessment: History and Physical, especially physical findings of rash, hypotension, respiratory distress. Labs are not used to diagnose due to the severe nature of illness.
Plan: Preserve airway and breathing, circulation, mentation. Evaluate for airway compromise. Epinephrine IM or IV depending on severity of presentation. Antihistamines as adjunct. Bronchodilators for bronchospasm.
Prognosis: Complete recovery common when anaphylaxis recognized early in the clinical course, to fatal if treated too late or with inadequate intervention. Allergist consult recommended after recovery

Phenotype development:

See discussion by @ericaVoss here Phenotype Phebruary Day 24 - Anaphylaxis

We debated if we wanted to limit to persons who did not have an environmental exposure to anaphylaxis. i.e. can perons who are in the anaphylaxis cohort due to the code ‘Bee sting-induced anaphylaxis’ the right phenotype of people for a safety surveilalnce study where anaphylaxis is the outcome.
Based on the clinical description (target) the person with Bee sting-induced anaphylaxis should be part of the target i.e. they have anaphylaxis.
There are many reasons to considered cohort definitions that allow and do not allow persons with Bee sting-induced anaphylaxis to enter the cohort of anaphylaxis.
So - we decided to develop and evaluate three different versions of anaphylaxis cohort definitions that leads to slightly different cohorts of persons.

Cohort Submission:

3 Cohort definitions are being submitted for peer review.
258 - Anaphylaxis of Anaphylactic Shock ( all events of anaphylaxis or anaphylaxis shock due to serum with no events in prior clean window.) ATLAS
259 - Anaphylaxis all cause (all events of anaphylaxis including due to vaccine exposure) ATLAS
221 - Anaphylaxis Non Environmental exposure related (all events of anaphylaxis that is not due to environmental etiology and no food, substance, insect bite or sting, poisoning as an explanation for anaphylaxis.) ATLAS

Phenotype development and evaluation for 258 is described in a post by @ericaVoss here Phenotype Phebruary Day 24 - Anaphylaxis . In summary, this post shows the rationale for the initial concept set expression of only snomed code anphylaxis without descendants and subsequent revision to include anaphylatic reaction due to serum.
259 is a broader clinicial idea, and includes food anaphylaxis. Anaphylaxis with Environmental exposures as the noted cause is still anaphylaxis - however, it may not be the type of anaphylaxis that is of interest for drug safety studies.
221 offers a definition of anaphylaxis that limits to anaphylaxis that is not reported to be associated with environmental exposure.

Potential problems with this phenotype:

  • Miss rate/False negative rate/Sensitivity - it is possible that mild forms may not be captured in the data, especially if they self-resolve. Also, anaphylaxis that co-occurs along with other serious conditions (e.g. heart failure, infections) may not be coded.
  • Index date misclassificaiton - we dont expect significant index date misclassificatio in acute settings, because persons who have anaphylaxis and receive care for anaphylaxis are likely to receive care on the same day. The exeception are persons who are coded for anaphylaxis but are not actively in anaphylaxis (e.g. problem list carry forward)
  • Specificity - persons with problem list carry forward may not have anaphylaxis on cohort start date. Differentiating anapylaxis based on etiology (environmental exposure vs drug exposure) maybe difficult.