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;

2)

1.

Type I : Anaphylactic, Atopic Reaction

2.

Type II : Cytotoxic Reaction

3.

Type III : Immune complex reaction

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 endplate, 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 antigenantibody (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 :Local : Arthus Reaction It is a localized inflammatory reaction, usually an

1.

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 virnsinfected 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 paraamino-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 singleuse 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 'epinephrineallergic' 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 (530 minutes).

Typical Reaction Progression of Generalized Anaphylaxis

1.

Early Phase : Skin Reactions

a.

Patient complains of feeling sick

2.

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

Associated with skin responses are various gastrointestinal or genitourinary

disturbances related to smooth muscle spasm :

3.

4.

a.

Severe abdominal cramps

b.

Nausea and vomiting

c.

Diarrhoea

d.

Local and urinary incontinence

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

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.
properties.

Most injectable histamine blockers have local anesthetic

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 :
PABCD
D (Definitive Care)

1.

Oral Histamine Blocker 50

mg.

disphenhydramine,

one

q6h

for

3+04

days

or

chherphemiramine.
2.

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

10

mg.

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
PABC
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).