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Anaphylaxis: Differential Diagnoses & Workup

Author: Richard S Krause, MD, Senior Faculty, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine
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Updated: Sep 2, 2009

Differential Diagnoses

Other Problems to Be Considered

Globus hystericus
Hereditary angioedema
Monosodium glutamate poisoning (ie, Chinese restaurant syndrome)

Workup

Laboratory Studies

• The diagnosis of anaphylaxis is clinical and does not rely on laboratory testing. When typical symptoms are noted in association with a likely exposure, diagnosis is virtually certain. Ancillary testing may help assess severity of reaction, although this is primarily a clinical judgment. When unclear, ancillary testing may help establish the diagnosis.
• The only potentially useful test at the time of reaction is measurement of serum mast cell tryptase, though the test's availability and slow turnaround time greatly limit its clinical utility. Tryptase is released from mast cells in both anaphylactic and anaphylactoid reactions. Levels are usually raised in severe reactions. Mast cell tryptase is raised transiently with blood levels reaching a peak approximately an hour after reaction onset.
  • Tryptase levels may aid in later diagnosis and treatment.
  • Consider the test in cases for which diagnosis of anaphylaxis is uncertain.
  • The utility of this test awaits full evaluation.
• Cardiac monitoring in patients with severe reactions and in those with underlying cardiovascular disease is important, particularly when adrenergic agonists are used in treatment. Pulse oximetry also is useful.

Imaging Studies

• Imaging studies are not generally useful in the diagnosis and management of anaphylaxis, although they may be used as diagnostic aids when diagnosis is unclear.

Other Tests

• Sensitivity testing
  • Testing for sensitivity to penicillin antibiotics may be useful when a penicillin or cephalosporin antibiotic is the drug of choice for a serious infection in a patient who has a history of severe allergic reaction. Obtain informed consent, and ensure that resuscitative equipment is immediately available. Protocols for acute testing for allergy to penicillin or cephalosporin antibiotics involve administration of increasing IV doses of the chosen antibiotic, while observing the patient for pruritus, flushing, urticaria, dyspnea, hypotension, or other manifestations of anaphylaxis. If no manifestations are observed, a full dose of the antibiotic may be administered safely.
  • A suggested protocol for IV testing begins with 0.001 mg of the chosen drug. At 10-min intervals, incrementally increase the dose (eg, 0.001 mg, 0.005 mg, 0.01 mg, 0.05 mg, 0.1 g, 0.5 mg, 1 mg, 10 mg, 50 mg, 100 mg, full dose), while observing the patient. Many other protocols exist. In most circumstances, perform desensitization on an inpatient basis. If the necessary resources are available, desensitization may be performed in the ED.

Procedures

• Intravenous contrast reaction prevention
  • Patients with a history of severe reactions to IV contrast material may require use of contrast in an urgent or emergency situation. Alternatives (eg, noncontrast spiral CT scan for ureteral stone, Doppler ultrasonography for deep venous thrombosis [DVT], nuclear scans for pulmonary embolism) should be considered but are not always feasible. In these circumstances, a prophylactic regimen of corticosteroids and antihistamines may be used. The precise efficacy of these regimens is difficult to evaluate, but they generally are considered effective. One author states that the recurrence rate for patients with a previous reaction was reduced from 17-60% to 9% when conventional contrast material was used; the rate was reduced to less than 1% when low osmolality material was employed after a pretreatment regimen.
  • The use of H2 blockers has not been shown to decrease the risk of reaction to IV contrast. One study suggests H2 blockers actually appear to increase the risk.
  • A widely quoted protocol for prevention of reactions to IV contrast suggests the following:
    • Use low osmolality contrast.
    • Administer hydrocortisone (200 mg IV); wait 2 hours if clinically appropriate.
    • Administer diphenhydramine (50 mg IM) immediately before the procedure.
• Desensitization regimens
  • Desensitization regimens for penicillin and cephalosporin antibiotic allergy have been shown effective. Because these regimens are lengthy (approximately 6 h), they have limited applicability to the ED. When patients wait for long periods in the ED or in an observation unit, consider desensitization regimens.
  • A typical desensitization regimen involves administering the antibiotic of choice in an initial dose of 0.01 mg. While observing the patient, double the dose every 10-15 minutes until a full dose has been administered.
  • Desensitization regimens do not protect against non-IgE-mediated reactions that may be severe or even life threatening (eg, Stevens-Johnson syndrome).
  • While theoretically attractive, premedication regimens have not been clinically shown to decrease incidence or severity of IgE-mediated allergic reactions to antibiotics.

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