ALLERGY IN ALABAMA n SPRING - FLOWERING GRASSES, ORNAMENTAL FLOWERS, NOT PINE POLLEN n FALL – RAGWEED NOT GOLDENROD n YEAR ROUND-ANIMAL DANDER AND SALIVA n SUMMER/HUMIDITY -MOLDS/ FUNGUS

RAGWEED GOLDENROD

Welcome to Alabama

Timothy Grass

Bermuda Grass

HYPERSENSITIVITY REACTIONS n TYPE I- ALLERGIC CONJUNCTIVITIS n TYPE II- MYASTHENIA GRAVIS n TYPE III-UVEITIS? SJOGRENS n TYPE IV- CONTACT DERMATITIS & GPC

Allergic conjunctivitis

Myasthenia Gravis

Sjogrens

Phlyctenular Conjunctivitis

ALLERGY CASCADE n IGE BINDS ANTIGEN n FORMS DIMER AT SURFACE OF MAST CELL n MAST CELL DEGRANULATES HISTAMINE PROSTAGLANDINS THROMBOXANES LEUKOTRIENES VASOACTIVE AMINES EOSINOPHIL ATTRACTING FACTOR

STAGES OF ALLERGIC DISEASE n EARLY PHASE u MAST CELLS AND PRODUCTS n LATE PHASE u LEUKOCYTES u T -LYMPHOCYTES n CHRONIC PHASE u T CELLS FACTORS

MAST CELLS n DIFFERENT TYPES OF MAST CELLS n CHYMASE POSITIVE n TYPTASE POSITIVE (all mast cells, most common ocular surface, prevents clotting) n CHYMASE AND TYPTASE (most common in non allergic)

calcium

Inside Mast Cells n Increase synthesis of phosopholipase A- production of arachodonic acid n Increase protein kinase production- necessary for degranulation n Increase in intracellular calcium levels n hours increase cytokine production

CGMP n INCREASES MAST CELL DEGRANULATION n ALPHA AGONISTS INCREASE u BY DECREASING CAMP n CHOLINERGICS INCREASE CGMP

CAMP n DECREASES DEGRANULATION n HISTAMINE INCREASES n BETA ADRENERGIC DRUGS INCREASE n ADENYL CYCLASE(PROSTAGLANDINS)

CAMPCGMP cAMP cGMP Balance

PROSTAGLANDIN D2 n PRIMARY OCULAR PG IN HYPERSENSITIVITY n CHEMOSIS n REDNESS n DISCHARGE n EOSINOPHIL CHEMOTAXIS

BIOLOGIC ACTIVITY OF PROSTAGLANDINS n PGF 2 & PGD 2 - BRONCHOSPASM n PGI 2 - PULMONARY DILATION & < PLATELET AGGREGATION n PGE 2 BRONCHODILATOR n PGE 1 &PGE 2 -> NERVE SENSITIVITY VASODILATION n TXA 2 -VASOCONSTRICTION

BIOLOGIC ACTIVITY OF LEUKOTRIENES n LTB 4 u PMN ATTRACTANT u EOSINOPHIL ATTRACTANT u > VASCULAR PERMEABILITY u >.EDEMA u COFACTOR W/ PGE 2 & PGD 2 n LTC 4, LTD 4, LTE 4 u BRONCHOCONSTRICTORS u MYOCARDIAL DEPRESSANTS

EOSINOPHILS-ACTIVATION n EOSINOPHIL CHEMOTACTIC FACTOR(LTB 4 ) n HISTAMINASE DECREASES n PHOSPHOLIPASE DECREASES n ARYL SULFATASE DECREASES n PLATELET ACTIVATING FACTOR STRONGLYATTRACTS

EOSINOPHILS n MAJOR BASIC PROTEIN (anti-parasite) u HIGHLY TOXIC TO EPITHELIUM u INCREASES MAST CELL DEGRANULATION n EOSINOPHIL CATIONIC PROTEIN n EOSINOPHIL PEROXIDASE

HISTAMINE n BRONCHOSPASM n VASODILATOR n INCREASES VASCULAR PERMEABILITY n ACTIVATES NERVE TERMINALS

PLATELET ACTIVATING FACTOR RELEASING CELLS n BASOPHILS n MAST CELLS n EOSINOPHILS n MONOCYTES/MACROPHAGES n PMN’S

T CELL MEDIATED FACTORS n IL-3 INDUCES MAST CELL DEGRANULATION n IL-4 FACILITATES I G E PRODUCTION BY B LYMPHOCYTES n IL-5 STIMULATES EOSINOPHIL PROLIFERATION

OCULAR RESPONSE IN ARACHADONIC ACID PATHWAY n CYCLO-OXYGENASE PATHWAY u LID SWELLING u CHEMOSIS u VASODILATION n LIPO-OXYGENASE PATHWAY u CHRONIC INFLAMMATION

OCULAR SURFACE HISTAMINE RECEPTORS n H 1 RECEPTORS- NEURONAL u PRODUCES ITCHING n H 2 RECEPTORS- VASCULAR u PRODUCES REDNESS

DIAGNOSIS OF ALLERGY n RAST (RADIOALLERGOSORBANT ASSAY) n PRICK TESTS n INDERATION TESTS n DIRECT CHALLENGE n CONJUNCTIVAL CHALLENGE

CONJUNCTIVAL CHALLENGE n FDA REQUIREMENT FOR NEW DRUGS n ALLERGEN APPLIED TO CONJ n REDNESS,WATERING,CHEMOSIS GRADED n RETEST WITH PRETREATMENT

DRUG ACTIONS n MAST CELL STABILIZERS n STEROIDS n ANTIHISTAMINES n ASPIRIN n NONSTEROIDALS n VASOCONSTRICTORS n THEOPHYLLINE

STEROID ACTIONS n DECREASE mRNA n INHIBITS PHOSPHOLIPASE A n POTENTIATES B ADRENERGICS n CONSTRICTS BLOOD VESSELS n DECREASES CHEMOTAXIS n LYMPHOPENIA n DECREASES MACROPHAGE FUNCTION u GI, RENAL, PLATELET, MACROPHAGE DIFFERENTIATION

STEROID EFFECTS n DECREASE MESSENGER RNA n INHIBITS PHOSPHOLIPASE A PRODUCTION n INCREASES CAMP n POTENTIATES B ADRENERGIC DRUGS n CONSTRICTS BLOOD VESSELS n DECREASES CHEMOTAXIS n LYMPHOPENIA n DECREASED MACROPHAGE FUNCTION

DRUG ACTIONS n STEROIDS-MULIPLE EFFECTS n MAST CELL STABILIZERS-INHIBIT CALCIUM ENTRY INTO CELL n ANTIHISTIMINES- EFFECT AFTER RELEASE n ASPIRIN - INHIBITS CYCLO- OXYGENASE PATHWAY n NONSTEROIDALS- INHIBIT CYCLO- OXYGENASE PATHWAY

COX 1 AND COX 2 n COX 1 PRESENT AT STEADY STATE LEVELS u HOMEOSTATIC FUNCTIONS n COX 2 ASSOCIATED WITH INFLAMMATION n VIOXX, CELEBREX, BEXTRA n PREFERENTIAL VS SPECIFIC

DRUG EFFECTS n VASOCONSTRICTORS -REVERSE VASODILATION n THEOPHYLLINE- INCREASE CAMP

FOOD ALLERGY n VARIABLE EFFECT DUE TO ABSORBTION n USUALLY LOCAL GI EFFECT n CAN BE IDIOSYNCRATIC

ALLERGIC SKIN REACTIONS n ERYTHEMA-REDNESS n FLARE-DIFFUSE REDNESS AROUND WHEAL n WHEAL-LOCALIZED EDEMA,TYPICAL LID u ANGIOEDEMA

DRUG ALLERGY n TOXICITY n INTOLERANCE n IDIOSYNCRATIC n ALLERGIC

IDIOSYNCRATIC REACTIONS n DIRECT MEDIATOR RELEASE n DIRECT ACTIVATION OF BIOLOGIC SYSTEM n ENZYME DEFECT n UNDERLYING DISEASE n SIMILAR TO ANAPHYLAXIS?

Anaphylaxis

TREATMENT OF ALLERGY n AVOIDANCE n THERAPEUTIC AGENTS u CHRONIC u ACUTE n IMMUNOTHERAPY

Effects of Immune Therapy