19: Allergy

Chapter 19


Allergic diseases are increasing in prevalence and are contributing significantly to health care costs. For example, the number of children with allergies has recently doubled.< ?xml:namespace prefix = "mbp" />1

One of the most common medical emergencies that can occur in the dental office is that of an acute allergic reaction. Accordingly, a requirement for every dental practitioner is a basic understanding of the pathophysiology of such reactions, as well as risk factors and clinical manifestations. In this context, such knowledge will permit meeting the following goals of safe and effective dental treatment:

    To identify patients with a true allergic history, so acute medical emergencies that might occur in the dental office because of an allergic reaction can be prevented
    To recognize head, neck, and oral tissue changes that might be caused by an allergic reaction
    To identify and plan appropriate dental care for patients who have severe alterations of the immune system secondary to irradiation or drug therapy or related to an immune deficiency disorder
    To recognize signs and symptoms of acute allergic reactions and to manage these problems appropriately

An overview of the significant principles of allergic disease, including the various types of reactions that may be encountered in the dental office, is presented.


Epidemiology: Incidence and Prevalence

Allergy is an abnormal or hypersensitive response of the immune system to a substance introduced into the body. It is estimated that 15% to 25% of all Americans demonstrate an allergy to some substance, including about 4.5% who have asthma, 4% who are allergic to insect stings, and 5% who are allergic to one or more drugs. Allergic reactions account for about 6% to 10% of all adverse drug reactions. Of these, 46% consist of erythema and rash, 23% urticaria, 10% fixed drug reactions, 5% erythema multiforme, and 1% anaphylaxis. About a 1% to 3% risk for an allergic reaction is associated with administration of any drug. Fatal drug reactions occur in about 0.01% of surgical inpatients and 0.1% of medical inpatients.14

Drugs are the most common cause of urticarial reaction in adults, and food and infection are the most common causes of these lesions in children. Urticaria occurs in 15% to 20% of young adults. In approximately 70% of patients with chronic urticaria, no etiologic agent can be identified.135

Use of iodinated organic compounds as radiographic contrast media results in about 1 death for every 1400 to 60,000 diagnostic procedures. Animal insulin used to treat patients with type 1 diabetes causes an allergic reaction in about 10% to 56% of these persons, and reports have stated that some 25% of patients with diabetes who are allergic to insulin react to penicillin.13

About 5% to 10% of people who are given penicillin develop an allergic reaction, and 0.04% to 0.2% of these experience an anaphylactic reaction to the drug. Death occurs in about 1% to 10% of those persons who experience an anaphylactic reaction. Usually, in anaphylactic reactions to penicillin, death occurs within 15 minutes after administration of the drug; 50% of the time, the allergic reaction starts immediately after drug administration. About 70% of affected patients report that they have taken penicillin previously (Box 19-1). The most common causes of anaphylactic death are penicillin, bee stings, and wasp stings; people with an atopic history are more susceptible to anaphylactic death than are patients with no history of allergy. Causes of anaphylaxis of significance in clinical practice are listed in Box 19-2.14


Box 19-1

Summary of 151 Cases of Penicillin-Related Anaphylactic Deaths

21 (14%) of the patients had a history of allergies.

106 (70%) of the patients had received penicillin before; of these, 25% experienced a sudden allergic reaction.

128 (85%) of patients died within 15 minutes of administration.

75 (50%) of the patients experienced symptoms right after first administration of the drug.

3 (2%) of the cases were related to oral penicillin.

Data from Idsoe O, et al: Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock, Bull World Health Organ 38:159-188, 1968.



Box 19-2

Causes of Human Anaphylactic Reactions of Importance in Health Care

Causative Agents

       Amphotericin B
    Miscellaneous Drugs/Therapeutic Agents
       Acetylsalicylic acid
       Protamine sulfate
       Nonsteroidal antiinflammatory drugs (NSAIDs)

Diagnostic Agents

    Sodium dehydrocholate
    Radiographic contrast media
    Benzylpenicilloyl polylysine (Pre-Pen)


    Synthetic adrenocorticotropic hormone (ACTH)



Blood Products

    Whole blood
    Gamma globulin
    Immunoglobulin A (IgA)


Data from Grammer LC, Greenberger PA (editors): Patterson’s allergic diseases, ed 7, Phildadelphia, 2009, Lippincott, Williams and Wilkins.


In rare cases, antihistamines have been reported to cause urticaria through an allergic response to the colored coating material of the capsule. In addition, azo and nonazo dyes used in toothpaste have been reported to cause anaphylactic-like reactions. Aniline dyes used to coat certain steroid tablets have caused serious allergic reactions as well.13

Parabens (used as preservatives in local anesthetics) have caused anaphylactoid reactions. Sulfites (sodium metabisulfite or acetone sodium bisulfite) used in local anesthetic solutions to prevent oxidation of the vasoconstrictors can cause serious allergic reactions. The group most susceptible to allergic reactions caused by sulfites includes the 9 to 11 million persons in the United States in whom asthma has been diagnosed.13 Allergy to latex occurs in between 1% and 6% of the general population, and much more commonly in persons who have spina bifida.4


Allergic diseases result from an immunologic reaction to a noninfectious foreign substance (antigen). They comprise a series of repeat reactions to a foreign substance. These reactions involve different types of immunologic hypersensitivity (Box 19-3) and elements of the nonspecific and specific branches of the immune system (Box 19-4). The three branches of the immune system are the humoral, cellular, and nonspecific branches. Functions of the humoral and cellular branches of the immune system are shown in Table 19-1.135


Box 19-3 Coombs and Gell Classification of Immunologic Hypersensitivity Reactions

Type I—anaphylactic or IgE-mediated

Type II—cytotoxic

Type III—immune complex–mediated

Type IV—cell-mediated or delayed

IgE, Immunoglobulin E.



Box 19-4

The Immune System

1 Nonspecific

    a Mechanical reflexes
       (1) Coughing, sneezing
       (2) Action of cilia
       (3) Sphincter control of bladder
    b Secretion of bactericidal substances
       (1) Stomach acid
       (2) Earwax (cerumen)
       (3) Enzymes in tears or saliva
    c Phagocytic cells
       (1) Neutrophils
       (2) Monocytes
       (3) Macrophages
    d Circulating chemicals
       (1) Complement
       (2) Interferon

2 Specific

    a Humoral immunity
       (1) Protection against bacterial infection
       (2) Clones of B lymphocytes
       (3) Recognition of chemical configuration
       (4) Production of antibodies by plasma cells
       (5) Eradication of antigen
    b Cellular immunity
       (1) Protection against viral infection, tuberculosis, leprosy
       (2) Transplant rejection
       (3) Production of cytokines by T lymphocytes
       (4) Eradication of antigen

Adapted from Thomson NC, et al, editors: Handbook of clinical allergy, Oxford, Blackwell Scientific, 1990, pp 1-36.


TABLE 19-1 Functions of the Immune System

Function Humoral Cellular
Processing of antigen T helper cells and macrophages Macrophages plus antigens of major histocompatibility complex (MHC)
Cellular recognition of antigen Receptors on B lymphocytes are sensitive to specific chemical configurations T lymphocytes with receptors to specific subsets of MHC antigens
Cellular response to presentation of antigen Specific clones of B lymphocytes multiply and produce plasma cells and memory cells Specific clones of T lymphocytes multiply and produce effector T cells and memory T cells
Cellular action against antigen Plasma cells produce specific immunoglobulins (antibodies); memory cells become plasma cells, with later antigen contact Effector T cells produce cytokines; Memory T cells become effector T cells, with later antigen contact
Eradication of antigen Reaction with specific antibody is facilitated by nonspecific branch of the immune system; antigen is removed by cells of a nonspecific branch Destruction of antigen by cytokines and elements of a nonspecific branch of the immune system

Adapted from Thomson NC, et al, editors: Handbook of clinical allergy, Oxford, Blackwell Scientific, 1990, pp 1-36.

Foreign substances that trigger hypersensitivity reactions are called allergens or antigens. Box 19-5 shows some of the characteristics of antigens. Two types of lymphocytes play central roles in the two branches of the specific immune system: B lymphocytes in the humoral branch, and T lymphocytes in the cellular branch. The three branches of the immune system do not operate independently. T lymphocytes play an important role in the regulation of B lymphocytes. The initial function of the humoral and cellular branches of the immune system involves the recognition of antigens; however, cells and chemicals from the nonspecific branch of the immune system are needed to eradicate antigens.13


Box 19-5


Materials considered foreign by the body

Large molecular size

Certain degree of molecular complexity

Cell-mediated immune response rarely induced by polysaccharides (T-independent antigens)

Multiple antigenic determinants or antibody-binding sites (epitopes)

Various reactions in humans

Adapted from Thomson NC, et al, editors: Handbook of clinical allergy, Oxford, Blackwell Scientific, 1990, pp 1-36.


Under some circumstances, repeated contact with or exposure to an antigen may cause an inappropriate response (hypersensitivity) that can be harmful or destructive to host tissues; thus, hypersensitivity reactions can involve cellular or humoral components of the immune system.14 Reactions that involve the humoral system most often occur soon after contact with the antigen; three types of hypersensitivity reaction (types I, II, and III) involve elements of the humoral immune system. Type IV hypersensitivity reactions involve the cellular immune system. Allergic reactions that involve the cellular immune system often have delayed onset. Examples include contact dermatitis, graft rejection, graft-versus-host disease, some drug reactions, and some types of autoimmune disease.135

Pathophysiology and Complications

Humoral Immune System

B lymphocytes recognize specific foreign chemical configurations via receptors on their cell membranes. For the antigen to be recognized by specific B lymphocytes, it must first be processed by T lymphocytes and macrophages. Each clone (family) of B lymphocytes recognizes its own specific chemical structure. Once recognition has taken place, B lymphocytes differentiate and multiply, forming plasma cells and memory B lymphocytes. Memory B lymphocytes remain inactive until contact is made with the same type of antigen. This contact transforms the memory cell into a plasma cell that produces immunoglobulins (antibodies) specific for the antigen involved. Box 19-6 lists the functions of the five classes of immunoglobulins. Note that immunoglobulin E is the key antibody involved in the pathogenesis of type I hypersensitivity reactions. Normal functions of the humoral immune system are shown in Box 19-7.135


Box 19-6

Functions of Immunoglobulins

1 Immunoglobulin (Ig)G

    a Most abundant immunoglobulin
    b Small size allows diffusion into tissue spaces
    c Can cross the placenta
    d Opsonizing antibody—facilitates phagocytosis of microorganisms by neutrophils
    e Four subclasses: IgG1, IgG2, IgG3, IgG4 (IgG can bind to mast cells)

2 IgA

    a Two types
       (1) Secretory (dimer, secretory components)—found in saliva, tears, and nasal mucus; secretory component protects from proteolysis
       (2) Serum (monomer)
    b Does not cross the placenta
    c Last immunoglobulin to appear in childhood

3 IgM

    a Large molecule
    b Confined to intravascular space
    c First immunoglobulin produced
    d Activates complement
    e Good agglutinating antibody

4 IgE

    a Very low concentration in serum (0.004%)
    b Increased in parasitic and atopic diseases
    c Binds to mast cells and basophils
    d Key antibody in pathogenesis of type I hypersensitivity reactions

5 IgD

    a Low concentration in serum
    b Little importance

Adapted from Thomson NC, et al, editors: Handbook of clinical allergy, Oxford, 1990, Blackwell Scientific, pp 1-36.



Box 19-7

Functions of the Humoral Immune System

1 First encounter with antigen (primary response)

    a Latent period
       (1) Antigen is processed
       (2) B lymphocyte clone is selected
       (3) Differentiation and proliferation
       (4) Plasma cells produce specific immunoglobulins
    b Specific immunoglobulin (Ig)M level increases first in serum followed by IgG
    c IgM levels later fall to zero
    d IgG levels fall; however, some stay the same

2 Second encounter with antigen (secondary response)

    a Latent period is shorter
       (1) Antigen is processed
       (2) Memory cells are selected; become plasma cells
       (3) Plasma cells produce specific immunoglobulins
    b IgM levels increase first
    c IgG levels increase to 50 times the level found in the primary response
    d IgM levels fall later
    e IgG levels fall later, but a significant serum level is usually maintained

Adapted from Thomson NC, et al, editors: Handbook of clinical allergy, Oxford, 1990, Blackwell Scientific, pp 1-36.


Type I, type II, and type III hypersensitivity reactions involve elements of the humoral immune system. Type I hypersensitivity is summarized in Box 19-8. This is an IgE-mediated reaction that leads to the release of chemical mediators from mast cells and basophils in various target tissues. The role of IgE is clear in such reactions, but that of the other sensitizing antibody, IgG4, is not well understood.135


Box 19-8 Type I Hypersensitivity

1 Immunoglobulin (Ig)E antibody–mediated

2 Immediate response

3 Usual allergens (antigens)

    a Dust
    b Mites
    c Pollens
    d Animal danders
    e Food
    f Drugs (haptens)

4 Symptoms

    a Anaphylaxis
    b Hay fever
    c Asthma
    d Urticaria, angioedema
    e Symptoms on occasion

5 Frequency: affects about 10% of the population

6 Inherited tendency


Type I Hypersensitivity Reactions

Type I hypersensitivity reactions commonly are caused by food substances (e.g., shellfish, nuts, eggs, milk), antibiotics, and insect bites (e.g., bee stings). They are related to the humoral immune system and usually occur soon after second contact with an antigen; however, many people have repeated contacts with a specific drug or material before they become allergic to it (Figure 19-1). The different types of type I hypersensitivity reactions are discussed next.


FIGURE 19-1 This generalized urticarial reaction occurred after injection of penicillin for treatment of an acute oral infection. The patient had previously taken penicillin a number of times without any problem.

Anaphylaxis is an acute reaction involving the smooth muscle of the bronchi in which antigen–IgE antibody complexes form on the surface of mast cells which causes sudden histamine release from these cells. The release of histamine, as well as other vasoactive mediators, leads to smooth muscle contraction and increased vascular permeability. The potential end result is acute respiratory compromise and cardiovascular collapse.

Atopy is a hypersensitivity state that is influenced by hereditary factors. Hay fever, asthma, urticaria, and angioedema are examples of atopic reactions. Lesions most commonly associated with atopic reactions include urticaria, which is a superficial lesion of the skin, and angioedema, which is a lesion that occurs in the deep dermis or subcutaneous tissues and often involves diffuse enlargement of the lips, infraorbital tissues, larynx, or tongue. In true allergic reactions, these lesions result from the effects of antigens and their antibodies on mast cells in various locations in the body. As is typical for type I hypersensitivity, the antigen–antibody complex causes the release of mediators (histamine) from mast cells. These mediators then produce an increase in the permeability of adjacent vascular structures, resulting in loss of intravascular fluid into surrounding tissue spaces—seen clinically as urticaria, angioedema, and secretions associated with hay fever.135

Of note, there are many types of angioedema. Three types of interest to dentistry are acquired (allergic-based), drug-induced, and hereditary angioedema. Drug-induced angioedema results from impaired bradykinin degradation after administration of certain drugs, such as angiotensin converting enzyme inhibitors. The hereditary form is due to a deficiency or dysfunction of complement C1 inhibitor, which can be triggered by trauma, thus leading to activation of the complement cascade and Hageman factor (factor XII) and overproduction of bradykinin.5

Type II Hypersensitivity Reactions

The key elements involved in type II hypersensitivity are shown in Box 19-9. These reactions are IgG- or IgM-mediated. The classic example of type II (cytotoxic) hypersensitivity is transfusion reaction caused by mismatched blood.135


Box 19-9 Type II Hypersensitivity

1 Antibody-mediated

2 Cytotoxic hypersensitivity

    a Antibodies combine with host cells recognized as foreign.
    b Foreign antigens bind to host cell membranes during induced hemolytic anemia or thrombocytopenia.

3 Common examples

    a Transfusion reactions from mismatched bloods
    b Rhesus incompatibility
    c Goodpasture’s syndrome


Type III Hypersensitivity Reactions

Type III hypersensitivity is summarized in Box 19-10. These reactions take place in blood vessels and involve soluble immune complexes. They constitute what is referred to as immune complex–mediated hypersensitivity. Their key feature is vasculitis. Clinical examples include systemic lupus erythematosus and streptococcal glomerulonephritis.135


Box 19-10 Type III Hypersensitivity

1 Antibody-mediated through immune complex formation

2 Also known as immune complex–mediated hypersensitivity

3 Local form is Arthus reaction

4 Immune complex formation

    a Hypersensitivity state: complexes persist and lodge in blood vessel walls, initiating inflammatory reaction.
    b Large complexes
    c Removed by neutrophils and macrophages
    d Soluble complexes (more antigen than antibody)
       (1) Most harmful
       (2) Penetrate vessel wall
Jan 4, 2015 | Posted by in General Dentistry | Comments Off on 19: Allergy
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