Allergy is an immune-mediated hypersensitivity reaction to a foreign antigen manifest by tissue inflammation and organ dysfunction. The clinical expression of allergic IgE-mediated disease depends on antigen exposure and host susceptibility manifesting as atopy. Atopic patients have an immunologic predisposition to several disorders: allergic rhinitis (see Chapter 8), allergic asthma (see Chapter 9), atopic dermatitis (see Chapter 6), and IgE-mediated food allergies. Although these disorders tend to aggregate in atopic families, each of these disorders may occur in individuals without personal or familial history of atopic disease. In addition, many mast cell– and IgE-dependent disorders (eg, many drug and chemical sensitivities, eosinophilic disorders, mast cell stability syndromes, chronic urticaria) occur with a similar incidence in atopic and non-atopic persons.
The timing of onset of allergic symptoms after exposure to a suspected allergen serves as a useful clinical marker on which to base diagnosis and treatment. Reactions are either immediate (occurring within 60–120 minutes after initial exposure) or delayed (occurring after several hours or up to several weeks after initial exposure) (eTable 20–3).
eTable 20–3.Classification of immunologically mediated hypersensitivity reactions. ||Download (.pdf) eTable 20–3. Classification of immunologically mediated hypersensitivity reactions.
|Classification ||Effector Mechanism ||Timing of Reaction ||Clinical Manifestations ||Associated Conditions |
|Type I (Immediate, IgE-mediated) || |
Crosslinking of IgE bound to FcεRs on mast cells causing degranulation and release of inflammatory mediators, eg, histamine, tryptase.
|Within 60–120 minutes || |
Anaphylaxis (see Table 20–13 for NIAID/FAAN criteria)
Rhinorrhea, sneezing, watery/itchy eyes
Wheezing, shortness of breath
|Type II (IgG- or IgM-mediated) || |
Direct IgG/IgM binding to antigen/hapten on cell surface leading to complement activation and cell destruction.
|Hours to days || |
Hemolytic anemia, thrombocytopenia, neutropenia
|Drug-induced, immune-mediated anemia, thrombocytopenia, neutropenia |
|Type III (Immune complex) || |
Deposition of antibody-antigen immune complexes in tissue capillary beds resulting in complement activation, leukocyte recruitment and inflammation.
1–3 weeks following antigen exposure
|Fever, arthralgia, rash, lymphadenopathy, glomerulonephritis, vasculitis || |
Serum sickness associated with drugs and venom
|Type IV (Delayed, cell- mediated) || |
Antigen-mediated T-cell activation leading to recruitment of leukocytes, release of inflammatory mediators including cytokines and cell cytotoxicity/cell death.
Typically 48–72 hours following antigen exposure
Rash (typically maculopapular), bullous exanthema, hepatitis
Allergic contact dermatitis
Delayed-type drug rash