Allergic Rhinitis

1. Allergic Rhinitis Dr. Dinesh Kumar, Assistant Professor, ENT, GMC Amritsar

2. Definition Allergic rhinitis is clinically defined as a symptomatic disorder of the nose induced by an IgE-mediated inflammation after allergen exposure of the membranes lining the nose

3. Natural History • Onset is common in childhood, adolescence and early childhood . • Symptoms often wane in older adults, but may develop or persist at any age

4. Natural History • No apparent gender selectivity or predisposition to developing AR • May contribute to a number of other conditions

5. Allergic rhinitis • Inflammatory disorder of nasal mucosa, characterized by pruritus, sneezing, rhinorrhoea and nasal congestion. • Adversely affects social life, school performance, and work productivity; especially in patients with severe disease • Loss of productivity, missed school and work days, and direct costs associated with treatment create substantial costs to society. Lancet 2011; 378: 2112–22

6. An Allergic Reaction

9. The Allergic reaction

10. Inflammatory cascade in allergic rhinitis Adapted from Indian J Chest Dis Allied Sci. 2003 Jul-Sep;45(3):179-89

11. How are the symptoms caused

12. Classical Symptoms

13. Other Manifestations

14. AR

15. Intermittent

16. Persistent

17. Mild

18. Moderate to Severe

19. Risk Factors for Allergic Disease

20. Allergic Shiners

21. Allergic Salute and Crease

22. Allergic Conjuctivitis

23. AR & Co-morbidities

24. Allergic rhinitis and diseases of the upper airway

25. Key factors important to normal PNS function

27. AR and Asthma Approx. 80% of patients with asthma have accompanying symptoms of rhinitis, and up to 60% of the patients with asthma have sinusitis

28. Possible Mechanisms by which RhinitisCould Provoke a Worsening of AsthmaPossible mechanism AR could provoke worsening of Asthma

29. Management of Allergic Rhinitis

31. First Generation Antihistamines • Rapid onset of action • Short half life • Significant relief from rhinorrhoea • Easily cross blood brain barrier

32. Side Effects

33. Second Generation AH • Improve selectivity • Hepatic and Cardiovascular side effects of terfanadineand astemizole • Non sedating • Demonstrated efficacy for AR symptoms

34. Wide Therapeutic Window of Second Generation Antihistamines • The second generation H1-antihistamines have a rapid onset of action with persistence of clinical effects for at least 24 hours, so these drugs can be administered once a day. • They do not lead to the development of tachyphylaxis and show a wide therapeutic window (e.g. fexofenadine)

35. Maximum Studied dose (Fexo 1380 mg) Not tested for adverse effects Ineffective Therapeutic Window Low H1-antihistamine dose High Minimally effective dose (Fexo 60 mg) Significance of wide therapeutic window (fexofenadine) Howarth PH. Advanced Studies in Medicine. 2004;4(7A):S508-512

36. Third Generation AH • Minimal side effects • Increased duration of action • Positive effect on nasal airflow • Reduction in nasal congestion

37. Effects of leukotrienes on airways • Increased levels in nasal fluid after allergen challenge • Contribute to both early and late phase • Nasal congestion • Sneezing, rhinorrhea • Chemoattractant for eosinophils • Promote eosinophil adhesion • Decrease eosinophil apoptosis

38. Leukotrine Inhibitors: • Competitively block binding of leukotrines to end organs. • Montelukast is only FDA approved Leukotrine inhibitor • Montelukast reduces exhaled Nitric oxide, a marker for airway inflammation • Montelukast works through LC C4 and D$ which are found in upper airway • Because Montelukast acts throughout the airway this agent is a good choice for those with concurrent Asthma and AR

39. Rationale for antihistamine-montelukast combination in AR • Histamine • Responsible for rhinorrhea, nasal itching and sneezing • Less evident effect on nasal congestion • Leukotrienes • Increase in nasal airway resistance and vascular permeability Blockage or inhibition of these two mediators may provide additional benefits compared to single mediator inhibition

40. Intra-nasal Steroids • Work mostly locally, thus avoid unwanted side effects associated with their oral or I/V use • • Newer formulations show even lower systemic absorption • • Most effective against late-phase mediators with some effect on acute phase response.

41. Intra-nasal Steroids • Should be used in a chronic manner • Higher dose results in greater benefit • Judicious use in children and pregnant women recommended • Large paed studies have not shown significant adverse effects

42. Intra-nasal Steroids • First line drug in seasonal AR • However for perennial AR management with I/N steroids alone has not proved to be as beneficial • Depending upon severity of disease short courses of oral steroids in addition to topical symptomatic relief more • Fewer side effects (IOP)

43. Drug and Symptom Matrix

44. Algorithm for management of AR Allergic Rhinitis Persistent Symptoms Intermittent Symptoms Moderate/Severe Moderate/Severe Mild Mild Intranasal Steroid • Oral H1 Blocker • Intranasal H1 Blocker • Leukotrine modifier • Intranasal Steroid • Oral H1 Blocker • Intranasal H1 Blocker • Nasal Cromone • Leukotrine modifier Follow up after 2 wks. Improved Failed In PAR Pt. FU after 2-4 wks. Review Dx Compliance Step down If failure step up, if improved continue for one month Rhinorrhea add Ipratropium Intranasal Steroid Itch/sneeze add H1 Blocker Blockage: add oral decongestant/steroid short term

45. Immunotherapy • Involves the sequential administration of antigen to patients with symptomatic, atopic conditions to induce tolerance to offending antigens • Effective in treatment of both AR & Asthma • Generally safe and well tolerated

46. Immunotherapy • Injectable: Popular in US • Sublingual: Popular in Europe • Intranasal: Under investigation

47. Selections of candidates for IT • Symptoms induced by allergen exposure • Patients with rhinitis and symptoms from lower airway during peak allergen exposure • Insufficient control of symptoms with AH and/or topical steroids

48. Summary… • Allergic rhinitis is associated with several co-morbidities and affects quality of life and productivity • Second generation antihistamines are recommended for treatment of allergic rhinitis in adults and children; fexofenadine has proven efficacy, is devoid of sedation and has wide therapeutic window • Leukotrienes play key role in allergic rhinitis; montelukast is most throroughly tested leukotriene antagonist

49. Summary • Antihistamine-montelukast combination seems to be a more effective strategy than monotherapy in the treatment of allergic rhinitis in patients with moderate to severe symptoms • Fexofenadine-montelukast combination yields significant reduction in nasal congestion and nasal resistance in allergic rhinitis vs. fexofenadine

50. Drug and Symptom Matrix