Contents

1. Introduction

2. Classification of the Allergic Diseases

3. Allergy to Local Anesthesia

i) Sodium Bisulfate Allergy

ii) Epinephrine Allergy

iii) Latex Allergy

iv) Topical Anesthetic Allergy

4. Clinical Manifestations

5. Signs and Symptoms

i) Dermatological Reactions

ii) Respiratory Reactions

iii) General Anaphylaxis

6. Allergy Testing

7. Dental Management of Allergy

Allergy

Introduction

Allergy is a hypersensitive state, acquired through exposure to a particular allergen,

re-exposure to which producers a weightened capacity to react. Allergic reactions

cover a broad spectrum of clinical manifestations ranging from mild and delayed

responses occurring as long as 48 hours after exposure to the allergen, to immediate

and life-threatening reactions developing within seconds of exposure. Allergic

diseases are a common and increasing cause of illness, affecting between 15% and

20% of the population at some time.

The pathogenesis of allergic reactions may be simplify viewed as variations of the

inflammatory response. Allergic reactions tend to involve more than one organ

system and to manifest a similar appearance from system to system.

Classification of allergic diseases according to source of antigen and origin of

response

I) Endogenous immune response to endogenous antigens.

A. Circulating antibody

1. Autoallergic hematologic diseases

2. Antibodies to tissue antigens in human diseases

B. Cellular (delayed) sensitivity

1. Experimental autoallergic disease

2. Human counterparts of experimental autoallergic disease

II) Endogenous immune response to exogenous antigens

A. Circulating antibody

1. Anaphylactic-type reactions

2. Atopic reactions

3. Arthurs reactions

B. Cellular (delayed) sensitivity

1. Tuberculin reaction

C. Grammatomartons hypersensitivity

1. Berylliosis

III) Exogenous immune response to endogenous antigens

A. Transfer of maternal antibody to fetus

1. Erythroblastosis betalis

2. Neonatal leukopenia Thrombocytopenia

3. Neonatal myasthenia gravis

B. Experimental transfer of antibodies

1. Masugi nephritis

C. Experimental transfer of cells

1. Graft-vs-host reactions

IV) Exogenous immune response to exogenous antigens

A. Experimental transfer of antibodies and antigens

1. Passive anaphylaxis

2. Passive arthurs reaction

B. Experimental transfer of cells and antigens

1. Tuberculosis reactions

2. Content dermatitis

V) Endogenous immune response to complex antigens (hapten-proteins)

A. Circulating antibody

1. Drug-induced blood dyscrasions

2. Drug-induced impus erythemartosus

B. Cellular sensitivity

1. Contact dermatitis

Gell and Goombs (1968) Classificaiton

Hypersensitivity Reactions Hypersensitivity may be defined as a state of

exaggerated immune response to an antigen. The lesions of hypersensitivity are

produced due to the interaction between antigen and product of the immune response.

Depending upon the rapidity and duration of the immune response, two distinct forms

of hypersensitivity reactions are recognised.

1) Immediate Type In which on administration of antigen, the reaction occurs

immediately (within seconds to minutes). Immune response in this type is

mediated largely by humeral antibodies. Immediate type of hypersensitivity is

further of 3 types;

1. Type I : Anaphylactic, Atopic Reaction

2. Type II : Cytotoxic Reaction

3. Type III : Immune complex reaction

2) Delayed Type In which the reaction is slower in onset and develops within

24-48 hours and the effect is prolonged. It is mainly mediated by cellular

response. Type IV is the delayed hypersensitivity reaction.

Type 1 : Anaphylactic, Atopic Reaction

Anaphylaxis is the opposite of prophylaxis. It is defined as a state of rapidly

developing immune response to an antigen to which the individual is previously

sensitized.

The response is mediated by humoral antibodies of IgE or reagin antibodies. IgE

antibodies sensitise basophils of pheripheral blood or most cells of tissues leading to

release of pharmologically-active substance called anaphylactic mediators. These

substances are histamine, serotomin, vasoactive intestinal peptide (VIP), chemotactic

factors of anaphylaxis for nentrophils and eosinophils, leukotrienses B4 and D4,

prostanglandins (thromboxane A2, prostanglandin O2 and E2) and platelet activating

factor. The effects of these agents are;

- Increased vascular permeability

- Smooth muscle contraction

- Early vasoconstriction followed by vasodilatation

- Shock

- Increased gastric secretion

- Increased nasal and lacrimal secretions

The clinical examples of anaphylax is may be of two types;

1. Systemic

2. Local

Systemic Anaphylaxis Eg.;

1. Administration of drugs eg. Penicillin

2. Administration of antiserum eg. anti-tetanus serum (ATs)

3. Sting by wasp or bee.

Clinical Features

- Itching

- Erythema

- Contraction of respiratory bronchioles

- Diarrhoea

- Pulmonary oedema

- Pulmonary haemorrhage

- Shock

- Death

Examples of Local Anaphylaxis

i) Hary fever (seasonal allergic rhinitis) due to pollen sensitisations of

conjunctiva and nasal passages.

ii) Bronchial asthma due to allergy to inhaled allergens like house dust.

iii) Food allergy to ingested allergens like cow's milk, fish etc.

iv) Cutaneous anaphylaxis due to contact of antigen with skin characterised by

nuticaria, wheal and flora.

v) Angioedema, an autosomal dominant inherited disorder characterised by

laryngeal oedema, oedema of eyelids, lips, tongue and trunk.

Local anaphlaxis is common, affecting about 10% of population. About 50% of these

conditions are familial with genetic predisposition and therefore also called atopic

reaction.

Type II : Cytotoxic Reaction

Cytotoxic reactions are defined as these reactions which cause injury to the cell by

combining humoral antibodies with cell surface antigens; blood cells being affected

more commonly. Three types of mechanisms are involved in mediating cytotoxic

reactions.

1. CYFOTOX IS ANTIBODIES TO BLOOD CELLS

This mechanism involves direct cytolysis of blood cells (red blood cells)

lencocytes and platelets) by combining the cell surface antigen with IgG or

IgM class antibodies. In the process, compliment system is activated

resulting in injury to the cell membrane. The cell surface is made susceptible

to phyocytosis due to coating or opsonisation from serum factors or opsomins.

i) Autoimmune Haemolytic Anaemia - In which the red cell injury is brought

about by autoantibodies reacting with antigens present on red cell surface.

Antiglobulin test (diret coombs test) is empheyed to detect the antibody on red

cell surface.

ii) Transfusion Reaction due to incompatible or mismatched blood

transfusion.

iii) Haemolytic disease of the newborn (Erythroblastosis foetatis) In which

the foetal red cells are destroyed by maternal isoantibodies crossing the

placenta.

iv) Idiopathic Thrombocytopenic Phapura (ITP) is the destruction of

platelets by autoantibodies reacting with surface components of normal

platelets.

v) Drug induced cytotoxic antibodies are formed in response to

administration of certain drugs like penicillin, methyl dopa, rifampicin, etc.

The drugs or their metabelites act as leptens binding to the surface of blood

cells to which the antibodies combine, bringing about destruction of cells.

2. CYTOTOXIC ANTIBODIES TO TISSUE COMPONENTS

Cellular injury may be brought about by auto antibodies reacting with some

components of tissue cells in certain diseases.

Examples are as under :-

1. Graves disease (primary hyperthyroidism) Thyroid auto antibody is

formed which reacts with the TSH receptor to cause hyperfunction and

proliferation.

2. Myasthemia graves Antibody to acetylcholine receptors of skeletal muscle

is formed which blocks the neuromuscular transmission at the motor end-

plate, resulting in muscle weakness.

3. Male Sterility Antisperm antibody is formed which reacts with spermatozoa

and causes impaired motility as well as cellular injury.

4. Antibody-dependent cell-mediated cyfotoxicity (ADCC) is cytotoxicity

by this mechanism is mediated by leucocytes like monocytes, neutrophils,

cosinophils and NK cells. The antibodies involved are mostly IgG class. The

cellular injury occurs by lysis and antibody coated target cells through Fe

receptors on leucocytes. The examples of target cells killed by this

mechanism are tumour cells, parasites etc.

Type III : Immune complex Reaction

Type III reactions result from formation of immune complexes by direct antigen-

antibody (Ag-Ab) combination as a result of which the complement system gets

activated causing cell injury.

Two types of antigens can cause immune complex-mediated tissue injury.

1. Exogenous Antigens Such as infections agents (bacteria, viruses, fungi,

parasites) certain drugs and chemicals.

2. Endogenous Antigens Such as blood components (immunoglobulins,

tumour antigens) and antigens in cells and tissues (nuclear antigens in SLE).

Type II Reactions are of 2 types :-

1. Local : Arthus Reaction It is a localized inflammatory reaction, usually an

immune complex vasculitis of skin, in an intimidural with circulating

antibody. Large immune complexes are formed due to excessive of antibodies

which precipitate locally in the vessel wall causing fibrinoid necrosis.

Eg. Injection of antitetanus serum; and

- Farmer's lung in which there is allergic alveolitis in response to bacterial

antigen from monldy hay.

2. Systemic; circulating immune complex disease or serum sleekness

- After the antigen is introduced into the circulation, it initiates formation of

antibodies which react with antigen to form circulating Ag-Ab complexes.

- Following the deposition of Ag-Ab complexes is the tissues, there is acute

inflammatory reaction and activation of complement system with the

reoperation of the biologically active compounds such as chemotactic factors,

vasoactive amines and anerphylatoxins. The examples are;

i) Various forms of glomerulonephritis eg.;

- Acute glomerulonephritis

- Membranous glomerulonephritis

- Lupus nephritis

ii) Collagen disease

Eg. - SLE

- Polyarteritis nodosa

- Scleroderma

- Rheumartoid Arthritis

- Sjogren's syndrome

iii) Goodpasture's syndrome

iv) Arthritis occuring transiently during infections

v) Uveitis

vi) Skin diseases

Type IV : Cell-Mediated Reaction

This type of hypersensitivity is mediated by specifically sensitised T hymphocytes

produced in the cell-mediated immune response.

1. Classical Delayed Hypersensitivity

This is mediated by specifically sensitised CD4 + T cell subpopulation on contact with

antigen.

The classical example of delayed hypersensitivity is the tuberculin reaction. On

intradermal injection of tuberculin-protein (PPD), an unsensitised individual develops

no response (tuberculin negative). On the other hand, a person who has developed

cell-mediated immunity to tuberculin protein as a result of BCG immunisation or has

been exposed to tuberculous infection develops typical delayed inflammatory

reaction, reaching its peak in 48 hours (tuberculin positive), after which it subsides

slowly. Microscopically, mononuclear inflammatory cells in and around small blood

vessels and odema are seen.

Other Examples :

- Tuberculosis

- Tuberinteid leprosy

- Typhoid fever

- Contact dermatitis

2. T Cell-Mediated Cytotoxicity CD8+ subpopulation of T hymphonytes are

the cytotoxic T cells (T CTL) and are generated in response to antigen like virns-

infected cells, tumour cells and incompatible transplanted tissue or cells.

Allergy to Local Anesthesia

Allergy to local anesthetics does occur, but its incidence has decreased dramatically

since the introduction of amide anesthetics in 1940s. Brown and associates started,

the advent of the amino-amide local anesthetics which are not derivatives of para-

amino-benzoic acid markedly changed the incidence of allergic type reactions to local

anesthetic drugs. Toxic reactions of an allergic type to the amino amides are

extremely rare, although several cases have been reported in the literature in recent

years, which suggest that this class of agents can on rare occasions produces an

allergic type of phenomenon.

Allergic responses to local anesthetics include dermatitis (common in dental office

personnel), Bronchospasm (asthmatic attack), and systemic anaphylaxis.

Hypersensitivity to the ester type of local anesthetics Procanine, Propoxycaine,

Benzocaine, tetracaine and related compounds such as procaine penicillin and

procanamide is much more frequent.

Amide-type local anesthetics are essentially free of this risk. However, reports from

the literature and from medical history questionnaires indicate that allergy to amide

drugs appears to be increasing, despite the fact that subsequent evaluation of these

reports usually finds them describing case of overdose, idiosyncrasy, or psychogenic

reactions.

Of special interest with regard to allergy is the bacteriostatic agent methylparaben.

The parabens (methyl, ethyl, and prepyl) are inlcuded, as bacteriostatic agents, in all

multiple use formulations of drugs, cosmetics and some foods.

Dental local anesthetic cartridges available in the united states and canada are single-

use items and as such no longer contain paraben preservations.

Sodium Bisulfite Allergy

Allergy to sodium bisulfite or metabisulfite is being reported today with increasing

frequency. Bisulfites are antioxidants that are commonly sprayed into prepared fruits

and vegetables to keep them appearing fresh for longer time. People who are allergic

to bisulfites (most often steroid-dependent asthmatic individuals) may develop a

severe response (rbonchospasm). A history of allergy to bisulfites. A history of

allergy to bisulfites should about the dentist to the possibility of this same type of

response if sodium bisulfite or metabisulfite is included in the local anesthetic agent.

Sodium bisulfite is found in all dental anesthetic cartridges that contain a

vasoconstrictor but is not found in 'plain' local anesthetic agent.

In the presence of a documented sulfite allergy, it is suggested that a local anesthetic

solution without a vasopressor should be used if possible. No cross-allergenicity is

present between sulfites and the 'sulfa' type antibiotics (snefonamides).

Epinephrine Allergy

Allergy to epinephrine can't occur in a living person. Questioning of the 'epinephrine-

allergic' patient immediately reveals signs and symptoms related to increased blood

levels of circulating cartecholamines (tachycardia, palpitartion, sweating,

nervousness), likely the result of bear of receiving injections/release of endogenous

cartecholamines (epinephrine and non-epiepinephrine). Management of the patient's

fear and anxiety over receipt of the injection is in order in most of these situations.

Latex Allergy

The thick plunger (also known as the stopper or bung) at one end of the local

anesthetic cartridge and the thin diaphragm at the other end of the cartridge through

which needle penetrates, at one time contained latex.

Because of latex allergy is a matter of concern among all health care professionals,

the risk of provoking an allergic reaction in a latex-sensitive patient must be

considered. A review of the literature on latex allergy and local anesthetic cartridges

by Shojaei and Haas revals that latex allergn can be released into the local anesthetic

solution as the needle penetrates the aliophragm, but no reports to the latex

component of the cartridge containing a dental local anesthetic.

Dental cartridges presenting available in the United States and Canada are latex free.

Topical Anesthetic Allergy

Topical anesthetics posses the potential to include allergy. The most commonly used

topical anesthetics in dentistry are esters, such as benzocaine and tetracanine.

The incidence of allergy to this classification of local anesthetics for exceeds that of

amide local anesthetics. However, becense benzocaine an ester topical anesthetic is

poorly absorbed systemically, allergic response that develop in response to its use

normally are limited to the site of application. When other topical formulations, ester

or amide, that are absorbed systemically are applied to mucous membrane, allergic

responses may be localized or systemic. Many contain preservatives such as methyl

paraben, ethyl paraben, or propyl paraben.

Clinical Manifestations

Immediate reactions develop within seconds to hours of exposure. With delayed

reactions, clinical manifestations develop gours to days after antigenic exposure

immediate reactions, particularly type I, anaphylaxis, are significant. Organs and

tissues involvement in immediate allergic reactions include;

- Skin

- Cardiovascular System

- Respiratory System

- Gastrointestinal System

Generalized anaphylaxis involves all these systems. Type I reactions may involve

only one system, in which case they are referred to as localised allergy. Examples of

localised anasphylaxis and their 'targets' include bronchospasm and urticaria.

Signs and Symptoms

Dermatologic Reactions The most common allergic drug reaction associated with

local anesthetic administration consists of urticaria and angioedema. Urticaria is

associated with wheals, which are smooth, elevated patches of skin. Intense itching

(pruritus) frequently is present.

Angioedema is localised swelling in response to an allergen. Skin color and

temperature usually are normal (unless verticaria or erythema is present). Pain and

itching are uncommon. Angioedema mostly involves the bace, hands, feet and

genitalia, but it can also involves the lips, tongue, pharynx, and larynx.

Respiratory Reactions

Clinical signs and symptoms of allergy may be solely related to the respiratory tract,

or respiratory tract involvement may occur along with other systemic response. Signs

and symptoms of bronchospasm, the classic respiratory allergic response, include:

- Respiratory distress

- Dyspnea

- Wheezing

- Erythema

- Cyanosis

- Diaphoresis

- Tachycardia

- Increased anxiety

- Use of accessory muscles of respiration

Laryngeal edema, an extension of angio-neurotic edema to the larynx, is a swelling of

the soft tissues surrounding the vocal apparatus with subsequent obstruction of the

airway.

Generalized Anaphylaxis The most dramatic and acutely life threatening allergic

reactions is generalized anaphylaxis clinical death can occur within a few minutes (5-

30 minutes).

Typical Reaction Progression of Generalized Anaphylaxis

1. Early Phase : Skin Reactions

a. Patient complains of feeling sick

b. Intense itching

c. Flushing (Elythema)

d. Giant hives (urticaria) over the face and upper chest

e. Nausea and possibly vomiting

f. Conjunctivitis

g. Vasomotor rhinitis

h. Pilometer erection

2. Associated with skin responses are various gastrointestinal or genitourinary

disturbances related to smooth muscle spasm :

a. Severe abdominal cramps

b. Nausea and vomiting

c. Diarrhoea

d. Local and urinary incontinence

3. Respiratory Symptoms usually develop next

a. Substernal tightness or pain in chest

b. Cough may develop

c. Wheezing

d. Dysphea

e. Cynosis of the mucous membranes and nail beds.

f. Laryngeal edema

4. Cardiovascular system is next to be involved

a. Pallor

b. Light handedness

c. Palpitations

d. Tachycardia

e. Hypertension

f. Cardial dysrhythmias

g. Unconsciousness

h. Cardiac arrest

Allergy Testing

Intra Oral Challenge Test The protocol for intracutaneous testing for local

anesthetic allergy used at the ostrow school of dentistry of U.S.C. for the past 35 years

involves the administration of 0.1 ml of each of the following

- 0.9% NaCl

- 1% or 2% Lidocaine

- 3% mepivacaine

- 4% Prilocaine

Without methylparaben, bisulfites, or vasopressors. After the successful completion

of this phase of testing, 0.9ml of one of the previously meted local anesthetic

solutions that produced no reaction is injected intraorally via supra-periosteal

infiltration atraumatically above maxillary right or left premolar or anterior tooth.

This called an intraoral challenge test.

Dental Management in the presence of Alleged Local Anesthetic Allergy

When doubt persists concerning a history of allergy to local anesthetics, do not

administer these drugs to the patient. Assume that allergy exists.

Effective Dental Care

Dental treatment requiring local anesthesia should be postoponed until a thorough

evaluation of the patient's 'allergy' is completed.

Emergency Dental Care

Emergency Protocol No.1

The most practical approach to this patient is to promide no treatment of an invasive

nature. Arrange an appointment for immediate consultation and allergy testing. Do

not carry out any dental care requiring the use of injectable or topical anesthetis. For

incision and drainage of an abscess, inhalation sedation with nitrons oxide and oxygen

might be an acceptable alternative.

Emergency Protocol No.2

Use general anesthesia is place of local anesthesia. For management of a dental

emergency. When properly used, general anesthesia is a highly effective and

relatively safe alternative.

Emergency Protocol No.3

Histamine blockers used an local anesthetics should be considered if general

anesthesia is not available, and if it is deemed necessary to intervene physically in the

dental emergency. Most injectable histamine blockers have local anesthetic

properties. Diphenhydramine hydrochloride in a 1% solution with 1:100, 000

epinephrin & provides pulpal anesthesia for upto 30 minutes.

Management of the patient with confirmed allergy

Management of the dental patient with a confirmed allergy to local anesthetics varies

according to the nature of the allergy, if the allergy is limited to esters, amides may be

used, if the allergy does truly exist to an ester local anesthetic, dental treatment may

be safely completed via one of the following;

1. Administration of an amide

2. Use of instamine blockers

3. General anesthesia

4. Alternative techniques of pain control

a. Hypnosis

b. Acupuncture

Skin Reactions

Signs and symptoms developing 60 minutes eg. are mild skin and mucous membrane

reactions after the application of local anesthetic

Basic Management follows :

P A B C D

D (Definitive Care)

1. Oral Histamine Blocker -

50 mg. disphenhydramine, one q6h for 3+04 days or 10 mg.

chherphemiramine.

2. Patient should remain in the dental office till 1 hour before discharge.

Respiratory Reactions

i) Bronchospasm

P A B C position the conscious patient comfortably. A, B and C are

assessed.

D (definitive care)

1. Terminate treatment

2. Administer Oxygen

3. Administer epinephrine 1M in the vastus lateralis muscle (0.3 mg. if > 30 kg. :

0.15 mg. if < 30 kg.)

4. On recovery administer histamine blocker to minimize risk of replace 50 mg.

1M diphenydramine.

ii) Laryngeal Edema

P A B C

D (definitive care)

1. Epinephrine 0.3 mg. 1M in the vastus lateralis muscle. Every 5-10 minutes.

2. Activate EMS. Summon emergency medical assistance and administer

oxygen.

3. Histamine blocker 1M or IV 50 mg. diphenhydramine.

4. Perform cricothyrotomy.

Dilutions of Vasoconstrictors

The dilution of vasoconstrictors is commonly referred to as a ration eg. 1 to 1000

written 1:1000.

- A concentration of 1:1000 means that 1 g (1000 mg.) of solute (drug) is

contained in 100 ml of solution.

- Therefore, a 1:1000 dilution contains 1000 mg. in 1000 ml of 1.0 mg./ml of

solution (1000 ug/ml).

In local anesthetics solution, vasoconstrictors are further diluted;

- To produce a 1:10,000 concentration, 1 ml of a 1:1000 solution is added to 9

ml of solvent (sterile water), therefore, 1:10,000 = 0.1 mg/ml (100 mg/ml).

- To produce a 1:100,000 concentration, 1 ml of a 1:10,000 concentration is

added to 9 ml of solvent; therefore 1:100,000 = 0.01 mg./ml (10 ug/ml).