Hypersensitivity Disorders

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Hypersensitivity Disorders

Allergy
Author Credentials 

Farrah Siddiqui, MD
American Academy of Otolaryngic Allergy

 

Module Learning Objectives 
  1. Identify the four major types of hypersensitivity and recognize the clinical signs and symptoms of hypersensitivity disorders.
  2. Explain the pathophysiology behind type I hypersensitivity in detail.
  3. Be aware that allergy and atopy involve type I hypersensitivity and that severe type I hypersensitivity reactions (anaphylaxis) may be potentially fatal.
  4. Recognize that atopic disorders such as allergic rhinitis and asthma are chronic illnesses with significant incidence, burden and socioeconomic disparities.
Embryology
  1. Review development of immune system, including the role of T & B cells, thymus.
  2. Recognize that congenital immunodeficiency can alter immune system response.
  • DiGeorge syndrome
  • Bruton Aggamaglobulinemia
  • selective IgA deficiency
  • Wiskoot-Aldrich syndrome
  • chronic mucocutaneous candidasis

 

References

  1. Ryan M.  AAOA Allergy Primer:  Immunodeficiency.  Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S74-8. 
  2. Toskala E.  Immunology.  Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S21-7
  3. Simon AK, Hollander GA, McMichael A.  Evolution of the immune system in humans from infancy to old age.  Proc Biol Sci. 2015 Dec 22; 282(1821): 20143085
Anatomy
  1. Identify the cells, mediators and immune pathways involved in hypersensitivity with special emphasis on TH1 vs TH2 immune pathways, T helper cells, B cells, immunoglobulins, mast cell, basophils, histamine, leukotrienes and tryptase.
  2. Recognize that type I hypersensitivity can affect many different anatomic sites including the skin (urticaria), eyes (allergic conjunctivitis), nose (allergic rhinitis), paranasal sinuses (allergic fungal sinusitis), lungs (asthma), cardiovascular system (anaphylactic shock), gastrointestinal system (food allergy and anaphylaxis).
  3. Explain the basis of skin prick/intradermal testing in type I hypersensitivity, as well as serum specific IgE testing for type I hypersensitivity and recognize skin patch testing for type IV hypersensitivity.

 

References

  1. Toskala E.  Immunology.  Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S21-7
  2. Abbas AK, Lichtman AH, Pillai Shiv.  Hypersensitivity (Chapter 11). In: Basic Immunology 6th edition:  Functions and Disorders of the Immune System.  Philadelphia: Elsevier; 2020. p. 219-234.  
  3. Wise S et al.  International Consensus Statement on Allergy and Rhinology:  Allergic Rhinitis.   Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352.
  4. Leatherman BD.  Anaphylaxis in the Allergy Practice.  Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S60-5.
Pathophysiology
  1. Cite that type I hypersensitivity is basis for atopy and allergy including allergic rhinoconjunctivitis, asthma, atopic dermatitis, anaphylaxis, food allergy, drug allergy, venom allergy.
  2. Identify the different immune cells and mediators involved in type I hypersensitivity including early and late response.
  3. Recognize that subsequent exposure to allergen can lead to more severe hypersensitivity response, leading to anaphylaxis.
  4. Explain the basic pathogenesis of Type II, type III and type IV hypersensitivity reactions and that a failure of self-tolerance, can lead to autoimmune disorders such as Grave’s disease, rheumatoid arthritis, myasthenia gravis and SLE.
  5. Review common examples of illnesses associated with types II, III, IV hypersensitivity, especially ones that can manifest in the ear, nose, throat, skin and lungs.

 

References

  1. Abbas AK, Lichtman AH, Pillai Shiv.  Hypersensitivity (Chapter 11). In: Basic Immunology 6th edition:  Functions and Disorders of the Immune System.  Philadelphia: Elsevier; 2020. p. 219-234.  
  2. Toskala E.  Immunology.  Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S21-7
  3. Casale TB. Biologics and biomarkers for asthma, urticaria, and nasal polyposis. J Allergy Clin Immunol 2017; 139(5):1411-1421.
  4. Wise S et al.  International Consensus Statement on Allergy and Rhinology:  Allergic Rhinitis.   Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352.
  5. Leatherman BD.  Anaphylaxis in the Allergy Practice.  Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S60-5.

 

 

Incidence of Atopic Disorders
  1. Recognize that atopic disorders such as allergic rhinoconjunctivitis, asthma, food allergies and atopic dermatitis are increasing in incidence.
  2. Cite that health disparities exist due to socioeconomic and living conditions and how this can affect the burden of chronic atopic illnesses such as asthma. 
  3. Identify the importance of cockroach allergy in inner city pediatric asthma and allergic rhinitis.

 

References

  1. Wise S et al.  International Consensus Statement on Allergy and Rhinology:  Allergic Rhinitis.   Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352.
  2. Mims JW.  Epidemiology of Allergic Rhinitis.  Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S18-20. 
  3. Settipane RA, Schwindt C.  Chapter 15: Allergic rhinitis. Am J Rhinol Allergy. 2013 May-Jun;27 Suppl 1:S52-5. 
  4. Centers for Disease Control (CDC). Most Recent Asthma Data. Available: https://www.cdc.gov/asthma/most_recent_data.htm
  5. Pomés A et al.  Cockroach allergen component analysis of children with or without asthma and rhinitis in an inner-city birth cohort.  J Allergy Clin Immunol. 2019 Jun 12.

 

 

Genetics
  1. Recognize that there is genetic component to atopy/type I hypersensitivity including allergic rhinitis, asthma, food/drug allergies (especially anaphylaxis), so noting family history is important.
  2. Explain that specific HLA subtypes can increase risk for various hypersensitivity disorders (including I, II, III and IV).

 

References 

  1. Wise S et al.  International Consensus Statement on Allergy and Rhinology:  Allergic Rhinitis. Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352.
  2. Waage J et al.  Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.  Nat Genet. 2018 Aug; 50(8):1072-1080.
  3. Isidoro-Garcia M. PTGDR gene in asthma: a functional, genetic and epigenetic study. Allergy. 2011 Dec; 66(12):1553-62.
  4. Mims JW. Epidemiology of Allergic Rhinitis. Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S18-20.

 

 

Patient Evaluation
  1. Obtain focused history including HPI, past medical/surgical history, current medications, allergies, family, social history and review of systems.  Social history should include smoking, occupational exposure, pets, special environmental circumstances such as moving/flooding.  Review of systems should include special attention to symptoms of sleep apnea, asthma and cardiovascular risk factors which would make skin testing and/or immunotherapy more risky.
  2. Perform complete physical examination including evaluation of eyes for allergic conjunctivitis/shiners, skin for allergic creases, ears for eustachian tube dysfunction (ETD), nose for mucosal congestion/drainage/obstruction/turbinate hypertrophy, throat for cobblestoning/drainage/hoarseness, neck for lymphadenopathy, lungs for wheezing/asthma.  Perform nasal endoscopy and/or laryngoscopy where indicated.
  3. Evaluate any investigations patient has brought such as allergy testing, imaging, audiogram, sleep study, spirometry.
  4. Order adequate diagnostic studies such as allergy testing, audiogram, spirometry, polysomnogram.

 

References

  1. Franzese CB. AAOA Allergy Primer: History and physical examination. Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S28-31.
  2. Lee S.  Practical clinical approaches to the allergic rhinitis patient. Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S66-9.
  3. Settipane RA, & Schwindt C. Chapter 15: Allergic rhinitis. Allergic Rhinitis, Chapter 15. Am J Rhinol Allergy. 2013 May-Jun;27 Suppl 1:S52-5.
  4. Reisacher WR. Asthma and the otolaryngologist.  Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S70-3. 
  5. Brigham EP & West NE. Diagnosis of asthma: diagnostic testing. Int Forum Allergy Rhinol. 2015 Sep;5 Suppl 1:S27-30.
  6. Stachler RJ. Comorbidities of asthma and the unified airway. Int Forum Allergy Rhinol. 2015; 5 Suppl 1:S17-S22.
  7. Wise S et al. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352.

 

Measurements of functional status
  1. Explain that chronic type I hypersensitivity such as allergic rhinitis and asthma can lead to long-term health problems such as recurrent/chronic sinusitis, obstructive sleep apnea, ETD/hearing loss as well as permanent respiratory compromise due to asthma.
  2. Recognize that patients may need work up with spirometry in asthma, polysomnogram for sleep disordered breathing, nasal endoscopy and/or CT sinus imaging for sinusitis, laryngoscopy for hoarseness, audiogram/tympanometry in hearing loss.
  3. Identify validated functional surveys that can be utilized to monitor treatment as well as for research purposes, such as the Medical Outcomes Survey Short-Form 36 as well as the more allergy-specific Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ).

 

References

  1. Lee S.  Practical clinical approaches to the allergic rhinitis patient. Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S66-9. Wise S et al.  International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352.
  2. Reisacher WR. Asthma and the otolaryngologist Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S70-3.Brigham EP & West NE.  Diagnosis of asthma: diagnostic testing. Int Forum Allergy Rhinol. 2015 Sep;5 Suppl 1:S27-30.

 

 

Testing
  1. Recognize and summarize different methods of inhalant allergy testing for type I hypersensitivity including skin testing (epicutaneous vs. intradermal vs. combination) and specific IgE (in vitro) testing.
  •   Explain that skin testing utilizes wheal and flare response (histamine)
  • Cite that in vitro testing measures IgE levels
  • Recognize that a subset of patients with negative skin and negative serum specific IgE testing may have elevated nasal specific IgE levels, suggesting a localized allergic rhinitis which may still benefit from allergy treatment
  • Recognize newer component resolved or molecular testing for type I hypersensitivity, which can be utilized in more complex allergy patients to better identify allergens for immunotherapy and sometimes predict adverse reactions
  1. Review skin/in vitro testing and oral food challenges for food allergy and that food allergy can involve different types of immunoglobulin/hypersensitivity responses, but food-related anaphylaxis is IgE mediated type I hypersensitivity.
  2. Describe how basophil activation test (BAF) can be useful in hypersensitivity disorders including food and drug reactions.
  3. Develop basic understanding of blood tests for systemic illnesses such as Grave’s disease, sarcoidosis, SLE and other systemic type II-III hypersensitivity disorders.
  4. Recognize that patch testing can be done on the skin for type IV hypersensitivity.

 

References

  1. Wise S et al. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352.
  2. Marple BF & Mabry RL. Chapters 3 – 7. In: Quantitative Skin Testing for Allergy: IDT and MQT. New York:Thieme; 2006.  P.17-47.  
  3. Fornadley JA. Skin Testing for Inhalant Allergy. Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S41-5.
  4. Osguthorpe, JD. In vitro allergy testing. Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S46-50. 
  5. Sundquist BK, Yang B, Pasha MA. Experience in patch testing: A 6-year retrospective review from a single academic allergy practice. Ann Allergy Asthma Immunol. 2019 May;122(5):502-507
  6. Abbas AK, Lichtman AH, Pillai Shiv. Hypersensitivity (Chapter 11). In: Basic Immunology 6th edition: Functions and Disorders of the Immune System. Philadelphia: Elsevier; 2020. p. 219-234.  
  7. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immuno. 2001 May; 107(5):  891-6.
  8. Shu SA, Chang C, Leung PS. Common methodologies in the evaluation of food allergy: pitfalls and prospects of food allergyprevalence studies. Clin Rev Allergy Immunol. 2014 Jun; 46(3):198-210.

 

Pathology
  1. Describe the pathology behind wheal and flare reaction during allergy testing versus delayed response in patch testing for contact dermatitis. 
  2. Identify histopathology of chronic granuloma and recognize that this is an example of type IV hypersensitivity.

 

References

  1. Toskala E. Immunology. Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S21-7
  2. Luetkens JA et al. Pulmonary sarcoidosis shortly after spinal tuberculosis infection: a diagnostic challenge. BMJ Case Rep. 2014 Apr 11;2014. 

 

Case Studies
  1. AAOA members can register and view clinical insights modules on AAOA website. Immunology, Immunodeficiencies, Anaphylaxis and Food Allergy are available until 2020: https://www.immunopaedia.org.za/clinical-cases/hypersensitivity/adverse-event-following-routine-vaccination/​
Review Questions
  1. Is type I hypersensitivity a TH1 or TH2 response?
  2. What is the hygiene hypothesis and how does it relate to hypersensitivity?
  3. Which immunoglobulin plays a major role in type I Hypersensitivity?
  4. Which mediator is responsible for wheal and flare response during type I hypersensitivity, for example during skin prick testing?
  5. Which mediator can be measured to diagnose anaphylaxis within six hours of the acute reaction?
  6. What type of hypersensitivity reaction is involved in myasthenia gravis, Goodpasture’s syndrome as well as Grave’s disease?
  7. What type of hypersensitivity response is involved in a positive TB skin test?
  8. What type of hypersensitivity reaction is involved in the pathogenesis of serum sickness, systemic lupus erythematosus (SLE) and acute glomerulonephritis?
  9. What type of hypersensitivity reaction is the classic poison ivy rash?
  10. What are common methods of testing available for inhalant allergy?
  11. What is the overall incidence and prevalence of allergic rhinitis and asthma in the USA?  Are there any differences in patients of lower socioeconomic status living in the inner city?
  12. What further testing would you recommend to patient with seasonal allergies along with nasal obstruction, snoring and excessive daytime sleepiness?
  13. What is the gold standard testing method for food allergy?
  14. What is the histopathologic appearance of chronic granulomatous processes affecting the head and neck, such as sarcoidosis?
  15. How will spirometry results of a patient with chronic asthma differ from results of a patient with restrictive lung disease such as sarcoidosis or pulmonary fibrosis?