Anaphylaxis
Allergic reactions can be mild to life threatening. Anaphylaxis, by definition, is a sudden, severe, potentially fatal, systemic allergic reaction that can involve various areas of the body (such as the skin, respiratory tract, GI tract, and cardiovascular system). Symptoms occur within minutes to up to 2 hours after contact with the allergy-causing substance but, in rare instances, onset can be delayed for up to 4 hours. Anaphylactoid reactions represent the same process, but are triggered directly without the involvement of IgE molecules. The overall prevalence is 30/100,000 person years. The mortality rate is around 1%. Offending agents include foods, drugs, insect stings, and exercise, but in 20% of the cases, no cause can be found (idiopathic).
Table: Pathogenetic mechanisms and aetiology of anaphylaxis
| I IgE-mediated anaphylaxis (60%) |
| • Drugs: penicillins, cephalosporins, sulphonamides, tetracyclines, quinolones |
| • Foreign proteins: horse serum, egg albumin, insect venom, enzymes like papain, chymopapain, latex |
| • Food (30%): eggs, milk, wheat, soy, peanuts, tree nuts, shellfish, apple, peach |
| • Therapeutic and diagnostic agents: anaesthetic agents, muscle relaxants, hormones |
| • Allergen immunotherapy |
| • Exercise-induced anaphylaxis |
| II Immune complex-mediated anaphylaxis |
| • Blood and blood products |
| • Dialysis membranes |
| III Direct mast cell degranulation |
| • Opiates, quinolones, vancomycin, muscle relaxants |
| • Radio contrast media |
| IV Modulators of arachidonic acid metabolism |
| • Aspirin, indomethacin |
| V Idiopathic anaphylaxis |
| • Exercise |
| • Catamenial anaphylaxis |
| • Idiopathic anaphylaxis |
Pathogenesis
Anaphylaxis occurs as a result of degranulation of tissue mast cells and circulating basophils by both IgE-mediated and non-IgE-mediated immunological mechanisms. The resultant release in mediators accounts for the pathophysiological responses seen during anaphylactic reaction.
Clinical features
Anaphylaxis involves a number of organs and systems. The most common symptoms experienced by patients are cutaneous signs and symptoms, followed by respiratory signs and symptoms in nearly 60% of the affected (Table: Symptoms and signs of anaphylaxis). Cardiovascular signs and symptoms occur in 33% of the patients. The clinical manifestations in an episode vary widely and may depend on the subject’s sensitivity, as well as the amount and type of allergen encountered. The initial symptoms of numbness and tingling of the lips and itching can progress rapidly to generalized urticaria and angioedema and cardiorespiratory collapse. Death may occur within minutes, and it is usually caused by laryngeal oedema causing stridor, or severe hypotension. Anaphylactic reactions can be confused with other causes of acute onset of generalized urticaria or cardiorespiratory collapse (Table: Differential diagnosis of anaphylaxis). If there is any doubt regarding the diagnosis, blood should be taken for plasma histamine or serum tryptase levels. Elevated levels indicate mast cell degranulation, and confirm the diagnosis.
Table: Symptoms and signs of anaphylaxis
| Sense of cutaneous and internal warmth |
| Tingling |
| Flushing |
| Urticaria/angioedema |
| Metallic taste in mouth |
| Periorbital oedema, erythema |
| Wheeze/cough/hoarseness |
| Respiratory obstruction and dyspnoea |
| Difficulty in swallowing |
| Sweating |
| Syncope |
| Collapse |
| Abdominal pain |
| Nausea/vomiting/diarrhoea |
| Incontinence |
Table: Differential diagnosis of anaphylaxis
| • Myocardial infarction |
| • Pulmonary embolus |
| • Cardiac arrhythmia |
| • Vasovagal reaction |
| • Carcinoid syndrome |
| • Mastocytosis |
| • C1 esterase inhibitor deficiency |
| • Seizure disorder |
| • Factitious anaphylaxis |
The situation most commonly confused with anaphylaxis is vasovagal syncope. As vasovagal syncope can be due to parenteral injections, the confusion with anaphylaxis is more significant. The absence of flushing, pruritus, urticaria, and respiratory difficulties in the presence of bradycardia, and well-preserved blood pressure helps in making the differentiation.
Management
Emergency management of anaphylaxis relies on quick assessment and early treatment. Cardiorespiratory status should be assessed, as in any medical emergency, and appropriate actions should be taken. Once the diagnosis of anaphylaxis is made, epinephrine should be injected intramuscularly into the thigh, as this provides the most efficient absorption. If there is no response to several doses of intramuscular epinephrine, intravenous administration should be considered. Intravenous antihistamine and corticosteroids are given simultaneously. Drugs commonly used during anaphylaxis are outlined in Table: Drugs used in anaphylaxis. A short course of corticosteroids is often prescribed to reduce the risk of late-phase reaction, but evidence supporting this is insufficient.
Table: Drugs used in anaphylaxis
| Class of drugs | Agents |
| Adrenergic stimulants | Epinephrine |
| Isoprenaline | |
| Norepinephrine | |
| P2 agonists (nebulized) | |
| Dopamine | |
| Antihistamines | HI receptor blockers |
| H2 receptor blockers | |
| Xanthines | Aminophylline |
| Corticosteroids | Hydrocortisone |
| Prednisolone |
In most cases there is complete resolution of the reaction. However, continued monitoring is essential. If problems persist, further action is required depending on the clinical condition. Patients receiving certain drugs, such as beta blockers and angiotensin-converting enzyme inhibitors, are at increased risk of inadequate response to the standard treatment.
Patients who have had an anaphylactic reaction should be reviewed in the allergy clinic. If the cause was known, further education and advice on avoidance might be required. If the cause was not known, a detailed history and appropriate investigations reveal the cause in most cases. SPTs or determination of specific IgE helps to confirm the allergen suspected from the history. These include foods, insect stings, and some cases of drug allergies. A challenge may be required in some cases, but this should be done only by physicians experienced in these procedures.
Prevention
The dramatic and potentially fatal nature of anaphylaxis makes its prevention the primary clinical goal. Patients who have anaphylaxis should have their specific cause identified. Total abstinence from the inciting allergen is the best way to eliminate the risk of anaphylaxis. Patients with anaphylaxis should receive written instructions on allergen avoidance and cross-sensitive materials. Education must extend to lifestyles and activity modification. Patients who have experienced anaphylaxis should be discouraged from using angiotensin-converting enzyme inhibitors and beta blockers. Patients with exercise-induced anaphylaxis should be advised to exercise only in the morning after an overnight fast, as many of these patients require the ingestion of any food, or sometimes a specific food, prior to experiencing anaphylaxis.
Those who are at continued risk of inadvertent exposures (e.g. to foods, such as nuts), should carry self-injectable epinephrine and antihistamines, and be educated in its use. If exposure can not be avoided (e.g. to certain drugs, such as penicillin or insulin), desensitization can be attempted (Table: Methods for prevention of anaphylaxis). Desensitization involves administration of a known allergen or drug in incremental doses. Desensitization has to be carried out in a controlled environment, as systemic and even fatal reactions can occur. Allergen immunotherapy has been evaluated in various studies, and has been found to be particularly useful in Hymenoptera sensitivity. Immunotherapy has not proven to be useful in the treatment of food allergy or antibiotic-mediated anaphylaxis.
Pre-medication prior to interaction with a known inciting agent is useful in managing patients with sensitivity to radio contrast media. Patients suffering from idiopathic anaphylaxis are best managed with regular oral sympathomimetics, antihistaminics, and glucocorticoids.
Table: Methods for prevention of anaphylaxis
| • Allergen avoidance |
| • Patient education |
| • Epipen |
| • Desensitization |
| • Beta stimulants |
| • Allergen immunotherapy |
| • Pre-medication with glucocorticoids and antihistamines |
| • Regular oral sympathomimetics, glucocorticoids, antihistaminics in idiopathic anaphylaxis |
| • DNA vaccines |
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