Management of Allergic Rhinitis .pptx

Allergic Rhinitis

1. Allergic Rhinitis

2. Module contents This module is split into 5 sections:

3. Burden of Allergic Rhinitis

4. Allergic Rhinitis Epidemiology AR represents a global health problem affecting 10-20% of the worlds population 1 Almost 30% of adults and 40% of children are affected 2 World-wide the prevalence of allergic rhinitis continues to increase 2 References Brozek J et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2010 Revision. Allergy 2010; 9/8/2010: S1-153 Wallace DC et. J Allergy Clin Immunol 2008; 122: S1-84

5. Prevalence of clinically confirmed allergic rhinitis in North America/Europe References: 1. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Taskforce on Practice Parameters in Allergy, Asthma, and Immunology. Ann Allergy Asthma Immunology 1998;81:478-518 2. Bauchau V et al. Eur Respir J 2004; 24: 758-764 Country Prevalence (95% CI Canada 20-25% 1 United States 10-30% Belgium 28.5% 2 France 24.5% Germany 20.6% Spain 21.5% Italy 16.9% UK 26.0%

6. IMPAIRED WELL BEING 1 DISRUPTED SLEEP LETHARGY DAILY ACTIVITIES IMPAIRED LEARNING & COGNITIVE FUNCTIONS DISTURBED REDUCED WORK & SCHOOL PRODUCTIVITY Social and economic impact of allergic rhinitis Reference: 1. Canonica GW et al. Allergy 2007: 62 (Suppl. 85): 17-25

7. Pathophysiology of Allergic Rhinitis

8. Pathophysiology of AR The early and late phase responses of the allergic cascade, including the inflammatory cells involved, mediators released and resulting symptoms: 1 1. Production of IgE by B cell in response to T cell cytokine secretion 2. Binding of IgE to receptors on mast cells 3. Re-introduction of antigen 4. Cross-linking of bound IgE 5. Mast cell activation 6. Release of mediators (Histamine, Leukotrienes, Cytokines, Chemotactic functions, Enzymes) 7. Appearance of Basophils, Eosonophils, Monocytes Reference: 1. Naclerio R. Clinical manifestations of the release of histamine and other inflammatory mediators. J Allergy Clin Immunol 1999:103:S382-S385

9. Sensitization to allergens Antigen presenting cells (APCs) , such as dendritic cells in the mucosal surface, process allergens and present some peptides from allergens on the major histocompatibility complex (MHC) class II molecule. This MHC class II molecule and antigen complex take a role as the ligand of T-cell receptors on Naive CD4+ T cells , which result in differentiation of Naive CD4 + T cells to allergen-specific Th2 cell. Activated Th2 cells secret several cytokines , which induce isotype switching of B cells to produce specific IgE and proliferation of eosinophils , mast cells and neutrophils . Produced antigen-specific IgE binds to high-affinity IgE receptors on mast cells or basophils . Reference: 1. Yang-Gi Min. The Pathophysiology, Diagnosis and Treatment of Allergic Rhinitis. Allergy Asthma Immunol Res. 2010 April;2(2): 2010; 2: 65-76

10. Allergen-induced sensitization and inflammation

11. Early and late reactions When AR patients are exposed to allergens, allergic reactions develop in 2 different patterns according to time sequence. One is the early reaction , in which sneezing and rhinorrhea develops in 30 minutes and disappears . The other is the late reaction , which shows nasal obstruction approximately 6 hours after exposure to allergens and subsides slowly . The early reaction is the response of mast cells to offending allergens (type I hypersensitivity). Stimulated mast cells induce nasal symptoms by secreting chemical mediators such as histamine, prostaglandins and leukotrienes. In contrast to the early reaction, eosinophil chemotaxis is the main mechanism in the late reaction, which is caused by chemical mediators produced in the early reaction. Several inflammatory cells, eosinophils, mast cells and T cells migrate to nasal mucosa, break up and remodel normal nasal tissue, and these processes result in nasal obstruction which is the main symptom of AR patients. Reference: 1. Yang-Gi Min. The Pathophysiology, Diagnosis and Treatment of Allergic Rhinitis. Allergy Asthma Immunol Res. 2010 April;2(2): 2010; 2: 65-76

12. Neurogenic inflammation When respiratory epithelium is destroyed and nerve endings are exposed by cytotoxic proteins from eosinophils, sensory nerve fibers are excited by nonspecific stimuli and stimulate both sensory afferent and surrounding efferent fibers, the socalled retrograde axonal reflex. This makes the sensory nerve fibers secrete neuropeptides such as substance P and neurokinin A, which induce contraction of smooth muscles, mucous secretion of goblet cells and plasma exudation from capillaries. This process is called neurogenic inflammation. Reference: 1. Yang-Gi Min. The Pathophysiology, Diagnosis and Treatment of Allergic Rhinitis. Allergy Asthma Immunol Res. 2010 April;2(2): 2010; 2: 65-76

13. Non-specific hyperresponsiveness Non-specific hyperresponsiveness is one of the clinical characteristics of allergic inflammation. Due to eosinophilic infiltration and destruction of nasal mucosa, the mucosa becomes hyperactive to normal stimuli and causes nasal symptoms such as sneezing, rhinorrhea, nasal itching and obstruction. This is a non-immune reaction that is not related to IgE. Hypersensitivity to non-specific stimuli such as tobacco or cold and dry air as well as specific allergens increases in AR patients. Reference: 1. Yang-Gi Min. The Pathophysiology, Diagnosis and Treatment of Allergic Rhinitis. Allergy Asthma Immunol Res. 2010 April;2(2): 2010; 2: 65-76

14. Diagnosis of Allergic Rhinitis

15. Clinical Diagnosis Nasal discharge Blockage Sneeze/itch } Rhinitis definition 1 2 or more symptoms for > 1 hour on most days Allergic Rhinitis Non-Allergic Rhinitis (Infection/structural abnormality/ vasomotor/primary disease ) History Examination Investigations (directed) Reference: 1. Yang-Gi Min. he Pathophysiology, Diagnosis and Treatment of Allergic Rhinitis. Allergy Asthma Immunol Res. 2010 April;2(2): 2010; 2: 65-76

16. Clinical symptoms of allergic rhinitis Primary clinical manifestations Congestion Rhinorrhoea Itching Sneezing Ocular symptoms Watering/tears, itching, red eyes Other signs and symptoms include: Significant loss of smell (hyposmia or anosmia) Snoring, sleep problems Chronic cough Malaise Reference: ARIA 2008

17. Common co-morbidities: Asthma Allergic rhinitis usually precedes asthma 3 Treatment of allergic rhinitis may improve asthma control 2 ARIA promotes assessing everyone with allergic rhinitis for asthma 1 References Brozek J et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2010 Revision. Allergy 2010; 9/8/2010: S1-153 Wallace DC et. J Allergy Clin Immunol 2008; 122: S1-84 Koh YY. The development of asthma in patients with allergic rhinitis. Curr Opin Allergy Clin Immunol. 2003 Jun;3(3):159-64

18. Common co-morbidities: Rhinoconjunctivitis Incidence Ocular symptoms are common Rhinoconjunctivitis symptoms have been reported in more than 75% of patients with seasonal allergic rhinitis 1 Clinical significance Severely impairs QOL Often a forgotten aspect of care Reference 1. Wallace DC et al. J Allergy Clin Immunol 2008; 122: S1-84

19. Classification of Allergic Rhinitis

20. Allergic Rhinitis Classification ARIA Guidelines 1 Symptoms Frequency/duration Intermittent Persistent Severity Mild Moderate Severe Reference: 1. Brozek J et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2010 Revision. Allergy 2010; 9/8/2010: S1-153

21. ARIA Classification of Allergic Rhinitis Reference: ARIA 2007 1 All of the following One or more items Consecutive weeks Consecutive weeks

22. Treatment of Allergic Rhinitis

23. Allergen Avoidance Background Success of intervention measured by clinical improvement Strategy success influenced by individual host sensitivity to allergen Sensitivity differs betweens allergens Effectiveness Allergen avoidance decisions are complicated Studies do not show consistent reduction in symptoms or medication requirements Avoidance is clearly beneficial in allergy to domestic pets, horses and certain occupational allergens (laboratory animals, latex), where clinical trials are unnecessary. However, a number of measures designed to reduce mite exposure (the most common indoor allergen) have not shown the expected results Reference: 1.Adapted. Scadding GK et al. Clin Exp Allergy 2008; 38:19-42

24. Pharmacotherapy The goal of medical treatment is to reduce symptoms and use medications with few or no side effects . For seasonal allergies: start medications just before season begins and continue the medicines all through the season. For perennial allergies: may need to take medicines year round

25. ARIA Guidelines: Recommendations for Management of Allergic Rhinitis 2012 Rhinitis Management Revised ARIA 2012

26. ARIA = Allergic Rhinitis and its Impact on Asthma. Bousquet et al. J Allergy Clin Immunol . 2001;108 (5 suppl):S147. ARIA Guidelines: Recommendations for Management of Allergic Rhinitis Mild intermittent Moderate severe intermittent Mild persistent Moderate severe persistent Immunotherapy Allergen and irritant avoidance Intranasal decongestant (<10 days) or oral decongestant Second-generation nonsedating H1 antihistamine Leukotriene receptor antagonists Local cromone Intra-nasal steroid

27. Stepwise approach to management of allergic rhinitis Adapted from Bousquet J et al. J Allergy Clin Immunol 2001;108:S147 –S 334. AH, antihistamine; HRQoL, health-related quality of life; INS, intranasal corticosteroids INS added to non-sedating AH ± decongestant Short course of corticosteroids added to INS, non-sedating AH ± decongestant Non-sedating AH ± decongestant Step-down as symptoms improve: Reduce number of drugs Reduce dose Change therapy Mild intermittent symptoms Moderate persistent symptoms, bothersome Inadequate response to therapy, symptoms impact upon HRQoL, co-morbidities Immunotherapy if symptoms: Show inadequate response to therapy Prolonged Impact upon HRQoL Lead to co-morbid conditions

28. ARIA Guidelines for Treatment of Allergic Rhinitis Congestion Rhinorrhoea Itching/ Sneezing Duration INS +++ +++ ++/+++ 12 - 48h Oral antihistamines + ++ +++/++ 12 - 24h Oral decongestants + - -/- 3 - 24h Intranasal cromones + + +/+ 2 - 6h Anticholinergics - ++ -/- 4 - 12h Antileukotrienes ++ + -/- Not reported ARIA = Allergic Rhinitis and its Impact on Asthma; INS = intranasal steroids. Bousquet et al. Allergy . 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Bousquet et al. Allergy . 2008;63(suppl 86):8. Van Cauwenberge et al. Allergy . 2000;55:116 . “Corticosteroids are the most effective pharmacological treatment for allergic rhinitis” “The effect of topical corticosteroids on nasal blockage and their anti-inflammatory properties favor them above other treatments.”

29. Nasal Decongestants (oral/topical) Background 1 Relieve nasal congestion Cause nasal vasoconstriction and decreased oedema Duration of use for more than three to five days is usually not recommended, because patients may develop rhinitis medicamentosa or have rebound or recurring congestion. 2 Side effects Oral 1 Hypertension, headache, tremor, urinary retention, dizziness, tachycardia, & insomnia 2 Caution with caffeine and other stimulants Topical 1 Local stinging/burning Nasal dryness Sneezing References Wallace DC et. J Allergy Clin Immunol 2008; 122: S1-84 Bousquet J, Van Cauwenberge P, Khaltaev N; ARIA Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol . 2001;108(5 suppl):S147–S334

30. Oral Antihistamines Recommended for SAR and PAR 1 Reduce sneezing, rhinorrhoea and nasal and ocular pruritis but have less effect on nasal congestion 2 ARIA recommend new generation formulations which cause less sedation 3 Histamine is the most studied mediator in early allergic response. It causes smooth muscle constriction, mucus secretion, vascular permeability, and sensory nerve stimulation, resulting in the symptoms of allergic rhinitis. 4 Because the onset of action of is typically within 15 to 30 minutes and they are considered safe for children older than six months, antihistamines are useful for many patients with mild symptoms requiring “as needed” treatment. 5 References 1. Scadding GK et al. Clin Exp Allergy 2008; 38: 19-42 2. Dykewicz MS. J Allergy Clin Immunol 2003; 111: S520-9 3. Brozek J et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2010 Revision. Allergy 2010; 9/8/2010: S1-153 4. Alexander S. The pharmacology & biochemistry of histamine receptors. August 1996. http://www.nottingham.ac.uk/~mqzwww/histamine.html. Accessed November 19, 2009. 5. Lipworth BJ, Jackson CM. Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf . 2000;23(1):11–33

31. Intranasal corticosteroids are gold standard first-line therapy for moderate/severe allergic rhinitis. 1,2 Intranasal corticosteroids (INSs) are the most effective treatments available for allergic rhinitis (AR). 3 They have been shown to be superior to oral H 1 receptor antagonists for AR and have been designated as the treatment of choice for this condition. 3 The development of INSs is one of the best examples of molecular modification of drug structure and delivery to achieve an almost ideal therapeutic index. 3 Intranasal (INS) Steroids Treatments for Seasonal Allergic Rhinitis. http://www.ncbi.nlm.nih.gov/books/NBK153706 / Jaime A Lagos and Gailen D Marshall. Montelukast in the management of allergic rhinitis. Ther Risk Clin Manag. Jun 2007; 3(2):327-332 3. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications. H. Derendorf and E. O. Meltzer

32. Their onset of action is 30 minutes, although peak effect may take several hours to days, with maximum effectiveness usually noted after two to four weeks of use. 1 Symptom improvement has been noted within 1–2 days following administration. 2 Studies have demonstrated that nasal corticosteroids are more effective than oral and intranasal antihistamines in the treatment of allergic rhinitis. 1 Systemic corticosteroids, which were developed in the 1950s, are effective in treating AR, but the high risk of serious toxicity with long-term administration has hindered their usefulness. 2 Intranasal (INS) Steroids 1. DENISE K. SUR, MD, and STEPHANIE SCANDALE, MD, David Geffen School of Medicine, University of California, Los Angeles, California Am Fam Physician. 2010 Jun 15;81(12):1440-1446. 7. 2. Derendorf H, Meltzer EO. Molecular and clinical pharmacology of intra-nasal corticosteroids: clinical and therapeutic implications. Allergy . 2008;63(10):1292–130

33. Intranasal (INS) Steroids Effective in relieving nasal congestion, rhinorrhoea, sneezing and nasal itching 1 Recommended for SAR and PAR 2 Recommended to be administered regularly for optimal benefit 1 The mechanism of action for corticosteroids is that they bind to glucocorticoid receptors to stop the release of inflammatory cells and mediators of the allergic response. References: 1. Rosenwasser LJ. Am J Med 2002; 113 (9A) 17S-24S 2. Scadding GK et al. Clin Exp Allergy 2008; 38: 19-42  

34. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications Allergy Volume 63, Issue 10, pages 1292-1300, 8 SEP 2008 DOI: 10.1111/j.1398-9995.2008.01750.x http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2008.01750.x/full#f3 Glucocorticoid Receptor Affinity

35. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications Allergy Volume 63, Issue 10, pages 1292-1300, 8 SEP 2008 DOI: 10.1111/j.1398-9995.2008.01750.x http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2008.01750.x/full#f3 Careful attention needs to be paid to the potential for direct systemic drug exposure of potent corticosteroid agents The Congress of the European Academy of Allergology and Clinical Immunology in 2006 reported that Fluticasone Furoate has very high tissue binding affinity to human nasal tissue and, hence, low systemic absorption

36. ARIA Guidelines for Treatment of Allergic Rhinitis Congestion Rhinorrhoea Itching/ Sneezing Duration INS +++ +++ ++/+++ 12 - 48h Oral antihistamines + ++ +++/++ 12 - 24h Oral decongestants + - -/- 3 - 24h Intranasal cromones + + +/+ 2 - 6h Anticholinergics - ++ -/- 4 - 12h Antileukotrienes ++ + -/- Not reported ARIA = Allergic Rhinitis and its Impact on Asthma; INS = intranasal steroids. Bousquet et al. Allergy . 2003;58:192. Bousquet et al. Allergy. 2002;57:841. Bousquet et al. Allergy . 2008;63(suppl 86):8. Van Cauwenberge et al. Allergy . 2000;55:116 . “Corticosteroids are the most effective pharmacological treatment for allergic rhinitis” “The effect of topical corticosteroids on nasal blockage and their anti-inflammatory properties favor them above other treatments.”

37. ARIA Guidelines for INS Use in Allergic Rhinitis INS should be regarded as the first-line treatment for: Intermittent moderate-to-severe allergic rhinitis Persistent allergic rhinitis (mild and moderate-to-severe) INS should be given regularly, and in severe cases commenced before pollen season It may be preferable to begin INS treatment before symptom onset, and more effective when given continuously Bousquet et al. J Allergy Clin Immunol . 2001;108:1a. Bousquet et al. Allergy. 2008;63(suppl 86):8.

38. ARIA Guidelines for INS Use in Allergic Rhinitis: Patient Selection Considerations Pediatric patients Special care has to be taken to avoid the side effects Pregnancy INS have not been incriminated as teratogens and are commonly used by pregnant women Elderly INS at recommended dose have not been associated with an increased risk of fractures Athletes INS may be used in athletes (approved by the USOC) WADA = World Anti-Doping Agency; IOC = International Olympic Committee. USOC = United States Olympic Committee Bousquet et al. J Allergy Clin Immunol . 2001;108:1a. Bousquet et al. Allergy. 2008;63(suppl 86):8.

39. ARIA Guidelines for INS Use in Allergic Rhinitis: Duration of Therapy ARIA guidelines do not provide specific recommendations regarding the duration of therapy with an INS “INSs may be more effective when given continuously” Bousquet et al. J Allergy Clin Immunol . 2001;108:1a. Bousquet et al. Allergy. 2008;63(suppl 86):8.

40. AAAAI/ACAAI Guidelines for INS Use in Allergic Rhinitis INS may be considered for initial treatment of AR, because they provide significant symptom relief INS alleviate ocular symptoms associated with AR INS are particularly useful for the treatment of severe AR INS use on as-needed (PRN) basis may not be as effective as continuous use AAAAI = American Academy of Allergy, Asthma and Immunology ACAAI = American College of Allergy, Asthma and Immunology AR = allergic rhinitis. Wallace et al. J Allergy Clin Immunol . 2008;122:s1.

41. Actions of Corticosteroids

42. Intra-nasal steroids Local Side-effects Nasal irritation (propylene glycol/ benzalkonium chloride) Nasal bleeding/crusting Septal perforation (rare – advise to use device away from septum) Warn patients Avoidance with correct delivery technique May be related to device induced trauma No evidence of nasal tissue atrophy Reference 1. Kariyawasam H and Scadding G. Seasonal allergic rhinitis: fluticasone propionate and fluticasone furoate therapy evaluated. Journal of Asthma and Allergy 2010: 3 19–28 1

43. Intra-nasal steroids - systemic side effects Minimal absorption from nasal mucosa Up to 80% of intranasal dose swallowed 1 Extensive hepatic first-pass metabolism by cytochrome P450 system Minimal systemic levels No significant HPA suppression However, growth suppression has been demonstrated in children Second generation INS References 1. LaForce. J Allergy Clin Immunol 1999; 103: S388-96

44. Factors to consider with INS products Ease of delivery Once or twice daily dosing Odourless Taste Well tolerated Device factors 1 Easy to administer Patient preference 1 Reference Kariyawasam H, Scadding G.Journal of Asthma and Allergy 2010: 3 19–28

45. Immunotherapy Recommended in patients with IgE-mediated disease in whom allergen avoidance is either undesirable or not feasible or who respond inadequately to usual therapy 1 Recommended for SAR and PAR 1 Subcutaneous route or sublingual route Treatment decision on an individual case-by-case basis References 1. Scadding GK et al. Clin Exp Allergy 2008; 38:19-42