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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 Dendritic Cells Moncytes & Macrophages T- Cells Inflammatory Cells BLymphocytes Eosinophils Mast Cells Histamine Chemical Mediators Chemokines Cytokines Leukotrines Prostaglandins The Allergic reaction Sensitization Ig E Production Arming of mast cells Release of mediators Clinical effects Inflammatory cascade in allergic rhinitis Adapted from Indian J Chest Dis Allied Sci. 2003 Jul-Sep;45(3):179-89 How are the symptoms caused Irritation of free nerve endings Itching nerve endings Sneezing Increased mucus production Rhinorrhea Vasodilation Congestion Increased vascular permeability Oedema Classical Symptoms Repetitive Sneezing Nasal Congestion Watery Rhinorrhea Nasal Pruritus Other Manifestations Eye Symptoms Ear Symptoms Post nasal drip AR Intermitten t Persistent Classification Mild Moderate to Severe Intermittent <4 days/week < 4 weeks Persistent > 4 days /week > 4 weeks Mild Normal sleep No 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 Asthma Nasal Polyps URTI Sinusitis 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 mechanism AR could provoke worsening of Asthma PND Nasal Obstruction Nasobronchial refex 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) Maximum Studied dose (Fexo 1380 mg) Ineffective Therapeutic Window Low H1-antihistamine dose Not tested for adverse effects High Minimally effective dose (Fexo 60 mg) Howarth PH. Advanced Studies in Medicine. 2004;4(7A):S508-512 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 Drugs and Symptoms Antihistamines Anticholinergics (Ipratropium bromide) Corticosteroids Decongestants Mast Cell Stabilisers Antileukotrines Sneezing Itching Rhinorrhea Congestion ***** **** *** ***** ***** ***** *** *** ***** ***** *** * *** ** **** Algorithm for management of AR Allergic Rhinitis Persistent Symptoms Intermittent Symptoms Moderate/Severe Mild Moderate/Severe 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. If failure step up, if improved continue for one month Intranasal Steroid Itch/sneeze add H1 Blocker Rhinorrhea add Ipratropium Step down Review Dx Compliance 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 comorbidities 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 Drugs and Symptoms Antihistamines Anticholinergics (Ipratropium bromide) Corticosteroids Decongestants Mast Cell Stabilisers Antileukotrines Sneezing Itching Rhinorrhea Congestion ***** **** *** ***** ***** ***** *** *** ***** ***** *** * *** ** **** Place in therapy for antihistamine-montelukast combination Allergic rhinitis with nasal congestion Allergic rhinitis with moderateto-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.Anil Monga Dr.Vikas Kakkar Dr. K K Handa