Cause:Aspiration, ingestion (Nejm 1992;327:380), or parenteral use of drugs and other haptens, eg, penicillin, anesthetics, radiocontrast agents, ACE inhibitors, NSAIDs (Nejm 1994;331:1282); foreign antigens, eg, insect stings (Nejm 1994;331:523) including fire ants (Ann IM 1999;131:424), desensitization shots, semen (Ann IM 1981;94:459), peanuts (Nejm 2003;348:986); polysaccharides, eg, dextran. But sulfa antibiotic allergy does not incr likelihood of sulfa nonantibiotic reaction (Nejm 2003;349:1628)

Pathophys:Respiratory distress due to both upper tract edema and lower tract bronchospasm perhaps due to leukotrienes (Ann IM 1997;127:472), previously called slow reacting substance (SRS). Hypotension due to histamine, kinins, and perhaps leukotriene release. Diarrhea and gi sx may be due to serotonin. Several drug-induced types of reactions are not IgE mediated, eg, those by radiocontrast agents, ACE inhibitors, and NSAIDs (Nejm 1994;331:1282).

Increased incidence in atopic persons

Sx:Respiratory distress; vascular collapse; cutaneous rash/itch; gi nausea, vomiting, diarrhea, and pain especially if antigen taken po

Si:Upper or lower airway obstruction; vascular collapse; rash

Onset in ½-3 min, die in 15-120 min if going to; recurs in 28% if rechallenged (Ann IM 1993;118:161)

Respiratory or vascular collapse, death

Lab:

Chem:Serum tryptase increased? (Nejm 1987;316:1622)

Serol:RAST testing, 20% false neg compared to skin testing

Skin tests:Pos test is very specific at 0.1-1 µgm/mL if anaphylaxis truly present (Nejm 1994;331:523); whole insect preparations no use, pure venom very specific. Passive transfer: patient's serum sc to animal or volunteer, challenge at 24 h

Histamine release from basophils in vitro very specific, 20% false neg, expose to 0.1 µgm/mL venom

Rx:

Emergent:

• Tourniquet if practical and sc or im source; ice packs
• Support vital signs w iv fluids, O₂, neb
• Epinephrine 0.5-1 mg iv/io/im (in children, 10 µgm/kg, ie, 0.01 mL/kg of 1:1000 im) or smaller iv doses, repeat q 20-30 min
• Diphenhydramine (Benadryl) 25-50 mg (in children, 1 mg/kg) iv/im + cimetidine 300 mg iv
• Hydrocortisone 200-400 mg iv, or methylprednisolone 60-80 mg iv followed by prednisone 60 mg po qd × 2-3 d
• Aminophylline 9 mg/kg load, 0.7 mg/kg/h perhaps if bronchospasm

Preventive options:

• EpiPen home im epinephrine kit
• Desensitize with venom (Nejm 2004;351:668) for pts w systemic reaction (uriticaria, angioedema, or mre); 95% effective, × 3-5 yr then stop; better than whole-body extracts (Nejm 1990;323:1627). Most helpful in children, probably worth doing in adults in whom half will have a systemic (not just large local) reaction after a first if stung again
• Steroids: for IVP dye reaction (not true anaphylaxis since doesn't always recur after previous episode), 150 mg prednisone divided q24h beginning 18 h before and continuing 12 h after procedure helps (Ann IM 1975;83:159); or methylprednisolone 32 mg po 12 h and 2 h before dye exposure helps some but not all (Nejm 1987;317:845); or diphenhydramine 50 mg im × 1 (Ann IM 1975;83:277). New hyperosmolar agents 20 × as expensive but less vagal and cardiac depression and perhaps less anaphylactoid (rv—Nejm 1992;326:425, 431)
• Experimental anti-IgE monoclonal antibody (Nejm 2003;348:986) sc q 1 mo is effective against peanut anaphylaxis

For idiopathic anaphylaxis, prednisone 60 mg qd × 1 wk, then qod and decrease to 5-10 mg qod; plus hydroxyzine 25 mg tid helps decrease frequency and severity (Ann IM 1991;114:133)