Appendix 1: Drug Allergy

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TABLE A1–1: Classification of Allergic Drug Reactions

Type	Descriptor	Characteristics	Typical Onset	Drug Causes
I	Immediate (IgE mediated)	Allergen binds to IgE on basophils or mast cells, resulting in release of inflammatory mediators	Within 1 hour (may be within 1–6 hours)	Penicillin anaphylaxis, angioedema Blood products Polypeptide hormones Vaccines Dextran
II	Delayed; Cytotoxic	Cell destruction occurs because of cell-associated antigen that initiates cytolysis by antigen-specific antibody (IgG) and complement. Most often involves blood elements.	Typically >72 hours to weeks	Penicillin, quinidine, quinine, heparin, thiouracils, sulfonamides, methyldopa
III	Delayed; Immune complex	Antigen–antibody (IgG or IgM) complexes form and deposit on blood vessel walls and activate complement. Result is a serum sickness-like syndrome or vasculitis.	>72 hours to weeks	May be caused by penicillins, sulfonamides, minocycline, hydantoins
IV	Delayed; T Cell-mediated	Antigens cause activation of T lymphocytes, which release cytokines and recruit effector cells	>72 hours
	IVa	Th1 cells and interferon-γ, monocytes and eosinophils respond to the antigen	1–21 days	Tuberculin reaction, contact dermatitis
	IVb	Th2 cells, interleukin-4 and interleukin-5 respond to the antigen	1–6 weeks	Maculopapular rashes with eosinophilia
	IVc	Cytotoxic T cells, perforin, granzyme B, FasL respond to the antigen	4–28 days	Bullous exanthems; fixed drug eruptions
	IVd	T cells and interleukin-8 respond to the antigen	>72 hours	Acute generalized exanthematous pustulosis

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TABLE A1–2: Top 10 Drugs and Agents Reported to Cause Skin Reactions

	Reactions per 1000 Recipients
Amoxicillin	51.4
Trimethoprim–sulfamethoxazole	33.8
Ampicillin	33.2
Iopodate	27.8
Blood	21.6
Cephalosporins	21.1
Erythromycin	20.4
Dihydralazine hydrochloride	19.1
Penicillin G	18.5
Cyanocobalamin	17.9

Data from Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994;331:1272-1285.

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TABLE A1–3: Treatment of Anaphylaxis

Remove the inciting allergen, if possible.
Assess airway, breathing, circulation, and orientation. Support the airway.
Cardiopulmonary resuscitation: Start chest compressions (100/min) if cardiovascular arrest occurs at any time.
Administer epinephrine 1:1000 (adults: 0.3–0.5 mg; children: 0.01 mg/kg) IM in the lateral aspect of the thigh.
Place patient in recumbent position.
Administer oxygen 8–10 L/min through facemask or up to 100% oxygen as needed; monitor by pulse oximetry, if available.
Repeat IM epinephrine every 5–15 minutes for up to 3 injections if the patient is not responding.
Establish IV line for venous access. Keep line open with 0.9% saline solution. For hypotension or failure to respond to epinephrine, administer 1–2 L at a rate of 5–10 mL/kg in the first 5–10 minutes. Children should receive up to 30 mL/kg in the first hour.
Consider nebulized albuterol 2.5–5 mg in 3 mL of saline for lower airway obstruction; repeat as necessary.
In cases of refractory bronchospasm or hypotension not responding to epinephrine because a β-adrenergic blocker is complicating management, glucagon 1–5 mg IV (20–30 mcg/kg; maximum, 1 mg in children) given IV over 5 minutes.
Give epinephrine by ...

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