Anaphylaxis

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Chapter 58 Anaphylaxis

Anaphylaxis is a symptom complex accompanying the acute reaction to a chemical recognised as hostile. In the classical reaction the patient has been previously sensitised (immediate hypersensitivity or type 1 hypersensitivity), although the sensitising agent may be unknown. The term ‘anaphylactoid reaction’ is used to describe reactions clinically indistinguishable from anaphylaxis, in which the mechanism is non-immunological, or has not been determined. Recent consensus meetings have suggested the use of the term ‘anaphylactoid’ be discontinued and ‘anaphylaxis’ used to describe the symptom complex which may be either ‘non-immune’ or ‘immune’.¹ Non-immune anaphylaxis may be produced by direct drug effects, physical factors or exercise, and a causative agent cannot always be determined. The mediators involved are the same as those in other acute inflammatory responses such as sepsis, but the rate of release is more rapid and of shorter duration.

AETIOLOGY

Clinical anaphylaxis in hospital commonly follows injection of drugs, blood products, plasma substitutes, contrast media, or exposure to latex products or chlorhexidine. Outside hospital, ingestion of foods or food additives (especially peanut products) or insect stings may be more common causes than drugs.

Neugut et al.² estimated 1400–1500 deaths per year in the USA and between 3.3 and 40.9 million patients at risk. They estimated radiocontrast media and penicillin to be the greatest cause of death, with food and stings the next groups. In contrast a postmortem study of 56 deaths in the UK³ attributed 19 deaths to venoms, 16 to foods and 19 to drugs and radiocontrast media.

In anaphylaxis, sensitisation occurs following exposure to an allergenic substance, which either alone, or by combination with a protein or hapten, stimulates the synthesis of immunoglobulin E (IgE). Some IgE binds to the surface of mast cells and basophils. Later, re-exposure to antigen produces an antigen–cell surface IgE antibody interaction where two IgE molecules are bridged. This results in mast cell degranulation, and the release of histamine and other mediators, including interleukin, prostaglandins and platelet-activating factor. Histamine is responsible for the early signs and symptoms, but is rapidly cleared from plasma. The overall effects of the mediators are to produce vasodilatation, smooth-muscle contraction, increased glandular secretion and increased capillary permeability. The mediators act both locally and upon distant target organs.

Anaphylactoid reactions may be due to a direct histamine-releasing effect of drugs or other triggers on basophils and mast cells. The symptom complex may also be produced by other mechanisms. Some intravenous drugs and X-ray contrast media may activate the complement system. Plasma protein and human serum albumin reactions may be induced by either albumin aggregates or stabilising agent-modified albumin molecules. Other reactions, including those to dextrans and gelatin preparations, may be activated by non-IgE antibody already present in the plasma or osmotic factors (dextrose, mannitol).

The direct histamine-releasing effects of some drugs may produce reactions due to the effect of histamine alone, and such reactions are related to volume, rate and amount of infusion. Recent work suggests that the site of release of histamine may be important in its clinical effects. Drugs such as morphine and Haemaccel release histamine from skin alone,⁴ and are unlikely to produce symptoms such as bronchospasm, whereas drugs which produce release from lung mast cells (e.g. atracurium, vecuronium and propofol) may be more likely to produce bronchospasm.⁵ Direct histamine release is usually a transient phenomenon, but in some patients severe manifestations may occur, particularly with Haemaccel and vancomycin.

Anaphylactic reactions are usually seen in fit and well patients. It is likely that the adrenal response to stress ‘pretreats’ sick patients, and blocks the release and effects of anaphylactic mediators. The exception to this appears to be patients with asthma, in whom reactions to the additives in steroid and aminophylline preparations may occur, and this may be related to the reduced catecholamine response in asthma.⁶ Patients on β-blockers and with epidural blockade may be more likely to develop adverse responses due to histamine release, and this may also be related to reduced catecholamine responsiveness. Reactions occurring in these groups are more difficult to treat.