Definition

  • Anaphylaxis not explained by a proved or presumptive cause or stimulus; accounts for ~30-60% of cases of anaphylaxis in adults and ~10% of cases in children
  • It becomes a diagnosis of exclusion after other causes have been considered, such as foods, medications, exercise, food and exercise, insect stings or bites, mastocytosis, C1 esterase inhibitor deficiency/dysfunction, psychogenic reactions, and Munchausen anaphylaxis (intentional surreptitious ingestion of a known allergen)
    • May be followed by panic attacks that can be confused with anaphylaxis
    • May coexist with food allergy, exercise-induced anaphylaxis, chronic urticaria, food allergy
    • Fatalities have been reported

Initial Approach

  • Besides careful history, consider:
    • Careful physical exam for urticaria pigmentosa
    • Skin testing/sIgE to foods and drugs
      • Fresh food prick to prick SPT may be more sensitive than commercial extracts
    • sIgE to galactose-alpha-1,3-galactose
    • Baseline and acute phase serum tryptase
    • Baseline and acute phase 24 h urine for histamine metabolites, prostaglandin D2
    • Oral challenges
    • Peripheral blood c-Kit D816V mutation
    • Bone marrow examination in some cases

Idiopathic Anaphylaxis Classification (Patterson)


IA table.png




Management

Patterson


IA algorithm.png

Greenberger/Lieberman

  • Discontinue medications that may complicate treatment or worsen an event:
    • Beta-blockers
    • ACE-inhibitors and ARBs
    • MAO-inhibitors
    • Certain tricyclic antidepressants (e.g. amitryptiline)
  • Encourage carrying an epinephrine auto-injector and wearing identification jewelry

Initial Treatment
Refractory Treatment
  • Epinephrine IM
  • Cetirizine or other H1 antihistamine PO
  • Albuterol 2-4 mg PO BID (if tolerated)
  • Prednisone PO if episodes severe or frequent
    • 40-60 mg PO QD x 1-2 wk, then QOD x 1 mo, then taper by 5-10 mg monthly if the patient is not experiencing anaphylaxis
    • Lack of response to prednisone (e.g. at least 40 mg PO QD for 2 weeks) suggests USIA subtype (see above), and treatment often paradoxically worsens this subtype
  • LTRA PO
  • Cromolyn PO
  • Ketotifen 2 mg PO TID - may be useful if prednisone dependent
  • Azathioprone or tacrolimus PO
  • Omalizumab (limited evidence for use in literature)

Note:
  • Vast majority of patients with IA gradually improve, including patients who have frequent episodes and require prednisone for months or even 2-3 years



References