Idiopathic anaphylaxis

Author: V. Dimov, M.D., Allergist/Immunologist, Cleveland Clinic
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU, Fort Lauderdale

A 61-year-old female is in the allergy clinic for evaluation of suspected anaphylaxis. No history of asthma, allergic rhinitis, food allergy, or atopic dermatitis. She had a negative skin and blood tests for multiple food and airborne allergens. The total IgE was low normal at 20. She also had normal normal C-1INH levels (qualitative and quantitative), CBCD, CMP, ANA, and ESR.

She had 4 episodes of symptoms suggestive of anaphylaxis, always during the hot days of the summer, separated about one year apart. All episodes occurred outside with temperatures exceeding 80F. She felt throat discomfort, and teary eyes. During one of the episodes she felt tingling in the last two fingers of the left hand. Three of the episodes were related to consuming wine and salad. There was no significant improvement with epinephrine (EpiPen) use during the last episode. She was found to be slightly hypotensive and tachycardic in the ER after the last episode.

Past Medical History, Past Surgical History: Unremarkable.

Family Medical History: Several members with coronary artery disease (CAD).

Social History: 15-ppd smoking history, quit 2 years ago.

Current Medications: Epinephrine p.r.n.

Drug allergies: Reviewed. NKDA.

Review Of Systems: 12/14 systems were reviewed, negative apart from history of present illness above.

Physical Examination: Unremarkable.

Procedures done today: Spirometry showed FVC 60% and FEV1 61% of predicted, with normal shape of the flow volume curve.

What is the likely diagnosis?

Suspected idiopathic anaphylaxis. No evidence of FDEIA.

Differential diagnosis includes:

- CAD - she has a strong family history and some suggestive symptoms - throat tightness, tingling of the last 2 fingers of the left hand.

- COPD - she has a low FEV1 and a smoking history. No active symptoms.

- syncope symptoms

What would you suggest for management?

The diagnosis of exclusion is suspected idiopathic anaphylaxis - with triggers such as alcohol, heat, exercise (nonimmunological triggers that cause direct activation of mast cells). If tryptase is normal within 3 hours of any future event, anaphylaxis would be unlikely.

There are no symptoms of sulfite hypersensitivity or latex allergy. Food or airborne allergens are not likely to play a significant role (she had both a negative blood and skin test). There was no significant improvement with epinephrine use.

What lab work would you suggest?

Lab work for baseline tryptase level, CH50 and C4 was suggested.

The recommendations include:

- Pulmonary consult for COPD
- Cardiology consult for suspected angina equivalent vs. syncope
- if there are future attacks - obtain tryptase in the ER within 3 hours of the attack along with plasma and urinary histamine (instructions were provided to the patient)

Use epinephrine autoinjector (EpiPen or Auvi-Q 0.3) and call 911 if anaphylaxis develop. A follow-up in 1-3 months was suggested.

Summary

There are 4 broad groups with triggers of anaphylaxis:

1. Allergen triggers (IgE-dependent immunologic mechanism)

Foods, especially peanut, tree nut, shellfish, fish, milk, egg
Insect stings (eg, Hymenoptera venom) and insect bites (eg, kissing bugs, mosquitoes)
Medications (eg, beta-lactam antibiotics, some nonsteroidal antiinflammatory drugs [NSAIDs])
Biological materials, including allergens, allergen immunotherapy, monoclonal antibodies, vaccines to prevent infectious disease, and hormones (eg, progesterone)
Natural rubber latex
Food additives, including spices, insect-derived colorants (eg, carmine), and vegetable gums
Inhalants (rare), eg, horse dander
Human seminal fluid (rare trigger of anaphylaxis in women)
Occupational allergens (eg, stinging insects, natural rubber latex)

2. Immunologic triggers (IgE-independent mechanism)

IgG-dependent (rare) eg, to high molecular weight dextran, infliximab
Coagulation system activation

3. Idiopathic anaphylaxis

Consider the possibility of a hidden or previously unrecognized trigger
Consider the possibility of mastocytosis or a clonal mast cell disorder

4. Nonimmunologic triggers (direct activation of mast cells and basophils)

Physical factors (eg, exercise, cold, heat, sunlight/ultraviolet radiation)
Medications (eg, opioids, some NSAIDs)
Alcohol (ethanol)

Instructions for optimal collection and handling of blood samples for measurement of tryptase and histamine following suspected anaphylaxis

Tryptase (serum or plasma)

When to collect the sample: Blood should be collected between 15 minutes and 3 hours after symptom onset whenever possible; samples collected less 15 minutes or more than 3 hours after symptom onset are less likely to be informative.

How to collect the sample: Blood can be drawn using standard technique. Collect blood for serum (red top tube) or plasma (tube with heparin, citrate or EDTA). A minimum of 1 mL is recommended. For postmortem samples, collect blood from the femoral artery or vein, not the heart.

How to process the sample: Serum or plasma should be placed on ice and frozen as soon as possible. Samples should be shipped frozen by overnight courier if the assay cannot be performed on site.

Histamine (plasma)

When to collect the sample: Plasma for histamine levels should be collected between 5 and 15 minutes after symptom onset; samples collected less than 5 minutes or more than 15 minutes after symptom onset are less likely to be informative.

How to collect the sample: Pull blood manually (DO NOT use vacuum tubes) under gentle pressure through a 20 gauge or larger needle into a syringe containing either citrate or EDTA.

How to process the sample: Anticoagulated blood should be placed on ice and centrifuged to separate plasma from cells as soon as possible, and then the plasma frozen until ready to be analyzed.

The assay for total tryptase is standardized. The assay for histamine is not standardized. Plasma is used to avoid the artifactual release of histamine from basophils that can occur during blood clotting.

Anaphylaxis is common (1 in 20 adults), 50% never received epineprine, the majority have life-threatening reactions. Anaphylaxis represents a huge opportunity for clinical improvement (Wood, JACI, 2014).

References

Anaphylaxis: Confirming the diagnosis and determining the trigger(s). UpToDate, 2013.
Anaphylaxis: Rapid recognition and treatment. UpToDate, 2013.

Published: 08-20-2013
Updated: 09-17-2013