Immediate hypersensitivity

Immediate hypersensitivity is defined as "hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability."

Pathogenesis

Type 1 hypersensitivity is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. Exposure may be by ingestion, inhalation, injection, or direct contact. The difference between a normal immune response and a type I hypersensitive response is that plasma cells secrete IgE. This class of antibodies binds to Fc receptors on the surface of tissue mast cells and blood basophils. Mast cells and basophils coated by IgE are "sensitized." Later exposure to the same allergen, cross-links the bound IgE on sensitized cells resulting in degranulation and the secretion of pharmacologically active mediators such as histamine, leukotriene, and prostaglandin that act on the surrounding tissues. The principal effects of these products are vasodilation and smooth-muscle contraction.

The reaction may be either local or systemic. Symptoms vary from mild irritation to death.

Examples

• Allergic asthma
• Allergic conjunctivitis
• Allergic rhinitis ("hay fever")
• Anaphylaxis. Anaphaxis has no universally accepted definition, but is defined by the U.S. National Library of Medicine as "may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock."
• Angioedema which is defined as "swelling involving the deep dermis, subcutaneous, or submucosal tissues, representing localized edema. Angioedema often occurs in the face, lips, tongue, and larynx."
• Eosinophilia. An elevated total eosinophil count, or an increased percentage of eosinophils among other leukocytes.
• Urticaria (hives) which is defined as "a vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress."
• Food hypersensitivity, which may be overdiagnosed.

Treatment

There are minimal randomized controlled trials to guide treatment, especially for treating anaphylaxis.

Clinical practice guidelines for advanced cardiac life support by the American Heart Association provide treatment algorithms that are available at http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-143#SEC5.

One protocol that successfully treated 241 drug hypersensitivity reactions is:

• First, for patients who report reactions to beta-lactam antibioics, give skin tests and do not challenge patients with positive skin tests.
• Reactions without a decrease in blood pressure. Give 40 to 60 mg of prednisolone and then 10 mg of loratadine or cetirizine for 2 days.
• Reactions with anaphylaxis. Give 0.25 µg [sic? should this be 0.25 mg] of intramuscular epinephrine in addition to prednisolone or antihistamine. Repeat epinephrine every 15 minutes if necessary.
• Reactions with hypotension. Give plasma expanders as needed.

For treating anaphylaxis, in the absence of empiric evidence a review of six clinical practice guidelines found that:

• Epinephrine intramuscularly at doses ranging from 0.01 mg/kg up to 0.5 mg is recommended by all guidelines.
• Antihistamines (H₁) are recommended by all but one guideline. Most recommended diphenhydramine while one guideline recommended chlorphenamine. The one dissenting guideline is from Australia where the only parenteral antihistamine is promethazine. While this guideline does not recommend antihistamines, it allows oral, non-drowsiness-inducing antihistamines that do not act on other receptors for other amines (such as serotonin or catecholamines).
• Antihistamines (H₂) were not studied in this review.
• Glucocorticoids parenterally are recommended by all but two guidelines.