Implications on therapy. Prof. of Medicine and Allergy Faculty of Medicine, Cairo University

Transcription

1 Implications on therapy Dr. Hisham Tarraf MD,FRCP(Edinb.) Prof. of Medicine and Allergy Faculty of Medicine, Cairo University Need for better understanding Global health problem Impact on quality of life Economic burden Unawareness of underlying disease mechanisms Links with asthma Association with sinusitis and other co-morbidities e.g. conjunctivitis, otitis.

2 DEFINITION ALLERGIC RHINITIS A symptomatic disorder of the nose induced by allergen exposure leading to an IgE- mediated inflammation of the nasal membranes and characterized by one or more of the following symptoms: Nasal congestion Rhinorrhoea Sneezing itching Rhinitis induced by pollens is frequently accompanied by symptoms that involve the eyes. Symptoms such as itch and irritation of the throat may also be present. A vast number of children with persistent allergic rhinitis also suffer from asthma. Presence of concomitant asthma should always be considered and if present, adequetely treated.

3 Most children with rhinitis are sensitized to airborne allergens.. If conjunctivitis is also present, the proportion of sensitization increases to >90%. A runny nose or constant colds without any other symptoms of respiratory infection- in combination with exposure to common allergens- should point to an allergic origin Sensitization Stimulation Signaling Migration Activation Damage Repair MHC II T-cell receptor B lymphocyte Plasma cell maturation IgE switching Dendritic cell T H 2 lymphocyte Bone marrow IgE Eotaxins RANTES Eosinophils RANTES Basophils Adhesion molecules (ICAM-1) Mast cell Histamine LTs PGs Tryptase Exudation Vasodilation Endothelium Nasal epithelium APR Sneeze/Itch CNS/Peripher alnerves Rhinorrhea Mucosal edema CPR Cellular infiltration Eosinophils: MBP, ECP Basophils: Cytokines Chemokines T lymphocytes Macrophages Chronic nasal obstruction

4 presenting cell Dendritic cell B cell Monocytes Epithelial cells IL-3 Naïve Lymphocyte TH 2 Lymphocyte

5 T-lymphocyte IFN negative B-lymphocyte TH 1 TH 2 Positive B-cell IgE Y Y Y Ag Y Mast cell Mediators Cytokines Preformed Histamine Proteases Proteoglycans Chemotactic factors Newly formed Leukotrienes PAF Prostaglandins Thromboxanes

6 Histamine Prostaglandins leukotrienes ṃast cell TNF IL-6 Acute allergic symptoms Inflammation Hyperreactivity Chronic symptoms Release of CYTOKINES Mast cells..... eosinophils T-Lymphocyte Macrophage/ monocyte epithelial cells

7 EOSINOPHIL Chemoattractants: Mediators: LT-C4, PAF, ECF. Chemokines: RANTES, eotaxin. Adhesion molecules: Rolling (tethering): Selectins Transendothelial migration: Transendothelial migration:integrins/icam-1, VCAM-1.

8 5 5- Activation migration. Activation Survival... IL-3, GM-CSF eosinophils LTC4, PAF MBP, ECP EPO, EDN activated eosinophils 6 Tissue Damage

9 One Airway, One Disease Symptoms Correlate with the Early- and Late-Phase Responses in Allergic Rhinitis and Asthma Upper Airways (Allergic rhinitis) Score for nasal symptoms Sneezing Nasal pruritus Congestion Rhinorrhea Immediate (early) phase Late phase Lower Airways (Asthma) FEV 1 (% change) challenge Time post-challenge (hours) Time (hours) FEV 1 =forced expiratory volume in one second Adapted from Varner AE, Lemanske RF Jr. In: Asthma and Rhinitis. 2nd ed. Oxford: Blackwell Science, 2000: ; Togias A J Allergy Clin Immunol 2000;105(6 pt 2):S599 S604.

10 Mast cells IgE Histamine Leukotrienes Prostaglandins Bradykinin, PAF Immediate rhinitis symptoms: - Itch, sneezing - Watery discharge - Nasal congestion Allergen T-lymphocytes (mast cells) IL-3,IL 3, GM-CSF B-lymphocytes Eosinophils VCAM-1 Chronic ongoing rhinitis: - nasal blockage - Loss of smell - nasal hyperreactivity

11 Allergic Rhinitis Early-Phase Inflammatory Response (minutes-1 hour) CYTOKINES IL-1 IL-3 IL-6 TNF- HISTAMINE Histamine binds to H 1 receptors Histaminic response Sneezing Itchy, watery eyes Rhinorrhoea Nasal congestion Allergen Leukotriene C 4 Prostaglandin D 2 Tryptase CHEMOKINES IL-8 Eotaxin RANTES ADHESION MOLECULES P-selectin ICAM Promotes eosinophil and other cell migration and infiltration Nasal mucosa Allergic inflammatory response Nasal inflammation Nasal obstruction Difficulty breathing Tinnitus Late-Phase Inflammatory Response (4 24 hours)