Chapter 23

Allergic Conditions

Renqian Zhong

Content Content

• TYPES OF IMMUNOPATHOLOGICAL

HYPERSENSITIVITY

• DEFINITION OF ALLERGY

• DISEASE STATES

• METHODOLOGIES

TYPES OF

IMMUNOPATHOLOGICAL

HYPERSENSITIVITY

TYPES OF IMMUNOPATHOLOGICAL HYPERSENSITIVITY

Type Cell Types Involved Mediators ExamplesImmediate (I)

Mast cells with cooperation from basophils, eosinophils, mononuclear cells, and possibly platelets for the late response

Histamine, leukotrienes, platelet activating factor

Allergic rhinitis and asthma, insect venom hypersensitivity, penicillin hypersensitivity

Cytotoxic (II) Macrophages and neutrophils Complement and phagocyte-derived mediators (enzymes, oxidants, eicosanoids, etc.)

Goodpasture syndrome, ABO incompatability, thrombocytopenic purpura, myasthenia gravis

Immune complex (III)

Same as type II Same as type II Serum sickness, glomerulonephritis

Cell mediated (IV)

Lymphocytes, macrophages, and occasionally basophils

Cytokines Allergic contact dermatitis, the tuberculin reaction, graft-versus-host disease, chronic allograft rejection, possibly multiple sclerosis

DEFINITION OF ALLERGY

DEFINITION OF ALLERGY

• Clinicians usually reserve the term allergy to

apply to acquired hypersensitivities that have

an immune basis.

• Allergy usually is reserved for conditions

mediated by immunoglobulin E (IgE) and

lymphocytes.

DISEASE STATES

Rhinitis

（ Allergic Rhinitis）

Rhinitis

• Allergic rhinitis is one of the most prevalent

disease states in western civilization.

• Approximately 15% to 20% of the general

population is allergic as defined by positive skin

tests to inhaled aeroallergen(s) and clinical

symptomatology that results from exposure to

them.

Asthma

Asthma

• Asthma may be defined as a condition of

reversible obstructive airways disease in which

there is a high degree of airway hyperirritability

to agents such as methacholine and histamine.

• Asthma is best diagnosed by performing

spirometry and determining the patient's

reversibility with inhaled bronchodilators.

Allergic Asthma

• It was estimated that approximately 20% to 25%

of all asthmatics had an allergic component to

their disease.

• Allergy is a common feature of the childhood

asthmatic, and the severity of childhood asthma

is proportional to the number of positive skin

tests and the severity of the reaction to those skin

tests.

Occupational Asthma

• Occupational asthma also can occur in

response to low-molecular-weight chemicals

on an allergic or a nonallergic basis.

• Isocyanate sensitivity can be disabling and

can result in asthmatic symptoms recurring

hours after the initial exposure.

Urticaria and Angioedema

Idiopathic Urticaria and Angioedema

• It is possible that urticaria can be associated

with an IgE-mediated response, as in the

case of some forms of food and insect sting

hypersensitivity.

• Most cases of angioedema are from mast-cell

degranulation occurring in deeper dermal

tissues.

Hereditary Angioedema

• Hereditary angioedema (HAE) is a rare

condition resulting from the functional

absence of the C1 esterase inhibitor molecule.

• The clinical state presents with recurrent

orofacial and peripheral angioedema or with

acute abdominal crises of pain and diarrhea.

Insect Venom Hypersensitivity

Insect Venom Hypersensitivity

• Hymenoptera venoms from bees, wasps, and

ants are capable of stimulating the production

of specific IgE.

• Reexposure to these venoms can initiate an

IgE-mediated response that can result in

allergic symptoms including generalized

urticaria, oropharyngeal angioedema, asthma,

and anaphylactic shock.

Adverse Reactions

to Foods and Food Additives

Adverse Reactions to Foods and Food Additives

• The most common manifestations of IgE-

mediated hypersensitivity to food proteins are

nausea, vomiting, diarrhea, and urticaria and

angioedema occurring within minutes after

ingestion.

• Food hypersensitivity has been implicated in

the pathogenesis of some cases of atopic

dermatitis.

Atopic Dermatitis

Atopic Dermatitis

• Atopic dermatitis is a rather common disorder

occurring in up to 4% of the population.

• It is associated with an eczematous dermatitis

that can at times be generalized but tends to

concentrate in the flexures of the neck and

inguinal regions and in the popliteal and

antecubital fossae.

Allergic Contact Dermatitis

Allergic Contact Dermatitis

• Contact dermatitis refers to any dermatologic

condition that is triggered by contact with a

substance.

• Allergic contact dermatitis is from a

hypersensitivity triggered by a lymphocyte

recognizing the offending material as foreign (a

type IV response).

Drug Hypersensitivity

Drug Hypersensitivity

• Drug hypersensitivities may or may not have

an immune etiology. Certainly, the most

common cause of drug hypersensitivity is the

IgE-mediated hypersensitivity to penicillin

and its semisynthetic derivatives such as

ampicillin and dicloxacillin.

Hypersensitivity Pneumonitis

• Hypersensitivity pneumonitis refers to a group

of lung disorders having an immune etiology

that are often caused by the occupational

exposure to a sensitizing protein.

• Farmer's lung is a disorder triggered by the

inhalation of spores of Micropolyspora faeni or

thermophilic actinomycetes.

METHODOLOGIES

IgE-mediated Disease

Skin Testing

• Skin testing should be performed by personnel

trained in its application with supervision by

physicians experienced in the diagnosis of IgE-

mediated diseases.

• In persons suspected of having IgE-mediated

hypersensitivity to inhalants or foods, the

percutaneous or epicutaneous skin tests should

be applied first.

• The most commonly used methods to determine

total serum IgE include solid-phase immunoassay

with fluorescence detection, radiolabeled

immunoprecipitation, immunoplate enzyme-

linked immunosorbent assay (ELISA),

microparticle-enhanced immunoassay, and solid-

phase immunoassay with luminescence detection.

Total Serum IgE

Specific IgE

• The radioallergosorbent test (RAST) is the classic

method for determining specific IgE antibody.

• This method generally has been replaced by the

Immuno-CAP procedure, which uses an expanded

cellulose matrix with high ligand binding capacity

and enzyme based fluorescence detection.

Other in vitro Methods

• Other methods have been developed to

quantitate specific IgE in vitro.

• In vitro methods with multiple allergens coupled

to the support are available and can be used for

screening for atopy. These methods are slightly

less sensitive than using individual allergen tests,

but can be used in a cost effective manner.

Clinical States Where Skin Testing, Specific IgE Antibody and Total IgE Are Useful

The greatest utility for skin testing and

specific IgE antibody lies in their ability to

aid in the diagnosis of aeroallergen

hypersensitivity and the resulting conditions

of allergic rhinitis and asthma.

Cell-mediated Immunity (CMI)

Patch Testing

• Patch testing is the preferred method for

diagnosing allergic contact dermatitis that is

a result of a type IV hypersensitivity

response.

• Performance of this testing requires an

experienced investigator.

In Vitro Cytokine Production-1

• Various lymphokines, cytokines, and interleukins

(IL) can be measured in supernatants by enzyme-

linked immunoassay using commercially

available kits.

• Interferon-gamma and migration inhibition

factor are correlates of cell-mediated immunity.

IL-4 production is a correlate of IgE production.

In Vitro Cytokine Production-2

• Production of IL-2, interferon-gamma, and

tumor necrosis factor is typical of Th1

responses.

• Production of IL-4 and IL-13 are typical of

Th2 responses.

• IL-5 induces maturation of and is chemotactic

for eosinophils.