Allergic Diseases

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The term allergy refers to many different clinical disorders: 

 

Allergic Asthma Allergic Conjunctivitis
Rhinitis Anaphylaxis
Seasonal Allergic Rhinitis Food and Drug Allergy
Perennial Allergic Rhinitis Eczema
Atopic Dermatitis  

 

The scope and impact of allergic disease is significant.  It affects more than 20% of the population (Franzese et. al)2.  The cost of medications to treat it is over $8B per year (SZEINBACH et. al)1.  Before we can effectively treat these diseases, an accurate diagnosis must be made.  Does the patient really have an allergy or is it an upper respiratory infection?  If it is an allergy, what is the allergic trigger that causes the symptoms?   It is important to note that not every runny nose is allergy.  For example, the following can all lead to rhinitis symptoms:

 

  • Infection 
  • Vasomotor rhinitis
  • Nasal tumor
  • Anatomic abnormalities of the nose and sinuses 
  • Rhinitis medicamentosa
  • True allergic rhinitis

 

Often patients are given the diagnosis of allergy without a proper diagnosis.  This may lead to expensive and ineffective treatment.  For example, the use of anti-histamines in a health maintenance organization demonstrated that 65% received the drug although they did not have a true allergic disorder (SZEINBACH et al)1.

 

Classification of Allergy

 

For both diagnostic and therapeutic reasons, it is best to have an understanding of the immunopathological basis of the patient’s immune-based disease.  When an immune response leads to tissue damage, the term hypersensitivity is used.  Gell and Coombs divided these immune-based adverse reactions into four types of hypersensitivity.   These four types, called Gell-Coombs classes are distinguished primarily by the immune effector mechanism. 

 

Gell Coombs Classification of Hypersensitivity Reactions:

 

Type Immune Mechanism
                 

I                            

IgE-Mediated (Immediate Hypersensitivity)

 

Allergen cross-linking of IgE/FceRI on mast cells and release of mediators   (histamine, tryptase, etc)

 

II 

IgG/IgM Mediated

 

Antibody specific for a cell bound antigen; role of complement

 

III

Immune Complex Mediated 

 

Circulation of antibody-antigen complexes and tissue damage from inflammatory response

 

IV 

T – Cell Mediated (Delayed Hypersensitivity)

  Activated specific T cells and a cytokine driven pathology

 

 

However, hypersensitivity reactions may not always be this discrete and may be mixed.  In addition, the Type IV reactions have been further subdivided, especially for drug hypersensitivities (Riedl MA et.al.)5.  

 

Clinical Diagnosis of Allergy

 

The accurate diagnosis of Type I (IgE mediated) hypersensitivities (e.g. allergic asthma and rhinitis) involves the following:

 

  • Assessment of the clinical findings and symptoms
  • Analysis of the patient’s exposure history
  • Measurement of allergen-specific IgE 

The measurement of specific IgE can be done by skin test or in vitro blood test (Ahlstedt et. al).  The choice of method depends on the type of allergen involved and the preferences of the physician.  However, the following features tend to favor the use of an in vitro method for specific IgE testing:

 

  • Improved specificity and lack of interference
  • Standardization of allergens and methods across many labs
  • Ability to accurately quantify the specific IgE
  • Patient convenience, especially for children
  • Ability to determine epitope or component specificity

 

Treatment of allergic disease 

 

How does the measurement of specific IgE inform the appropriate treatment of allergic diseases?  The choices for treatment are:

o   Allergen avoidance

o   Pharmacotherapy

o   Immunotherapy

 

Avoidance of the allergen is the most effective treatment, if the offending allergen(s) can be identified and if it can practically be avoided. This is where the measurement of specific IgE, in combination with a careful analysis of exposure history can be extremely helpful. Generally, a regionalized panel of 6 – 10 pollens with a few specific perennial allergens (e.g. mites, dander, etc.) will be appropriate.

 

Food Allergy

 

The prevalence of food allergy in the U.S. is estimated to be in the 3.5 – 4.0% range, but surveys indicate that a much higher percentage of the public think that they have food allergy (Sampson).  Furthermore the estimated incidence of food anaphylaxis cases is 50,000 per year.  Immune-based adverse food reactions may or may not involve IgE antibody and can be cellular-based (Sampson)6,7.

 

Considerations in ordering food allergy tests

 

o    Importance of quantitative measurements

A number of recent studies have shown that the use of quantitative cutoffs are helpful in the prediction of allergic food reactions.  This can be important since the mere presence of specific IgE does not always mean that the patient will have clinical disease. (Sampson et. al)6,7

 

o    The concept of the specific activity of IgE to determine clinical significance of a positive IgE.  In addition to the concentration of food specific IgE, the affinity and the specific activity (ratio of specific to total IgE) are believed to be clinically important (Hamilton et. al.)3

 

 

 

The new frontier in allergy testing is that we can now further define the specificity of food specific IgE.  So-called “component resolved diagnosis” (i.e. molecular food allergy) is emerging as a breakthrough in allergy in general and food allergy in particular (Nicolaou et al.)4.

 

 

References

 

1. Szeinbach SL, Williams B, Muntedam P, O’Conner R. Identification of Allergic Disease Among Users of Antihistamines.JMCP. 2004;10(3):234-237.

 

2. Franzese, C. Diagnosis of Inhalant Allergies: Patient History and Testing. Otolaryngol Clin. 2004; 44: 612-623.

 

3. Hamilton RG, MacGlashan Jr. DW, Sarbjit SS. IgE antibody-specific activity in human allergic disease. Immunol Res. 2010;47:273-284.

 

4. Nicolaou N, MPhil, Poorafshar M, Murray C, Simpson A, Winell H, Kerry G, Harlin A, Woodcock A, FMedSci, Ahlstedt S, Custovic A. Allergy or 5. tolerance in children sensitized to peanut: Prevalence and differentiation using component-resolved diagnostics. J ALLERGY CLIN IMMUNOL. 2010; 125:191-7.

 

5. Riedl MA, Casillas AM. Adverse Drug Reactions: Types and Treatment Options. American Family Physician. 2003; 68(9):1781-1790.

 

6. Sampson HA, Ho DG. Clinical Aspects of allergic disease. Relationship between food-specific IgE concentrations and the risk of positive food 7. challenges in children and adolescents. J ALLERGY CLIN IMMUNOL. 1997;100(4):444-451.

 

7. Sampson HA. Update on food allergy. JALLERGY CLIN IMMUNOL. 2004;113(5):805-819.

 

8. Ahlstedt S. Understand the usefulness of specific IgE blood tests in allergy. Clin Exp All. 2002;32:11-16.