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

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

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

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

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

An Allergic Reaction

Inflammatory Cells Dendritic Cells T- Cells B- Lymphocytes Mast Cells Eosinophils Moncytes & Macrophages

Histamine Chemokines Cytokines Chemical Mediators Leukotrines Prostaglandins

The Allergic reaction SensitizationIg E Production Arming of mast cells Release of mediatorsClinical effects

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

How are the symptoms caused

Classical Symptoms Repetitive Sneezing Nasal Congestion Watery Rhinorrhea Nasal Pruritus

Other Manifestations Eye SymptomsEar SymptomsPost nasal drip

AR Intermitten t Persistent Mild Moderate to Severe Classification

Intermittent < 4 days/week < 4 weeks

Persistent > 4 days /week > 4 weeks

Mild Normal sleepNo impairment of daily activit No troublesome Symptoms in untreated patients

Moderate to Severe Abnormal Sleep Impairement of daily activity Abnormal work Troublesome Symptoms

Risk Factors for Allergic Disease Family History Season of Birth Male Gender during Childhood Increase in pollution Dietary Changes Obesity

Allergic Shiners

Allergic Salute and Crease

Allergic Conjuctivitis

AR & Co-morbidities Otitis Media URTISinusitis Nasal Polyps Asthma

Allergic rhinitis and diseases of the upper airway

Key factors important to normal PNS function Patency of ostia Function of ciliary apparatus Quality of secretions

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

Possible Mechanisms by which Rhinitis Could Provoke a Worsening of Asthma Possible mechanism AR could provoke worsening of Asthma Nasobronchial refex Nasal Obstruction PND

Management of Allergic Rhinitis Allergen Avoidance Pharmacotherapy Surgery Immunotherapy

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

Side Effects

Second Generation AH  Improve selectivity  Hepatic and Cardiovascular side effects of terfanadine and astemizole  Non sedating  Demonstrated efficacy for AR symptoms

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)

Significance of wide therapeutic window (fexofenadine) Low H 1 -antihistamine doseHigh IneffectiveTherapeutic Window Not tested for adverse effects Maximum Studied dose (Fexo 1380 mg) Minimally effective dose (Fexo 60 mg) Howarth PH. Advanced Studies in Medicine. 2004;4(7A):S

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

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

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

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

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.

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

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)

Drug and Symptom Matrix

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

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

Immunotherapy  Injectable: Popular in US  Sublingual: Popular in Europe  Intranasal: Under investigation

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

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

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

Drug and Symptom Matrix

Place in therapy for antihistamine-montelukast combination  Allergic rhinitis with nasal congestion  Allergic rhinitis with moderate- to-severe symptoms

Blessings from the Holy City…….

A very cordial invitation to all of you to the 5th AOIPBCON being organized at M K Hotel Amritsar on 13th and 14th April 2013.

Guest Faculty Dr. Renuka Bradoo Dr. Ashok Gupta Dr. Vikas Kakkar Dr. Anil Monga Dr. K K Handa