ALLERGIC DISORDERS Allergy an altered state of reactivity to common environmental antigens.

s. FEATURES OF ALLERGIC DISEASES: Allergens refers to an antigen that triggers an Ig E response in genetically predisposed individuals Type 2 Helper T cells secrete cytokines favoring Ig E synthesis and are involved in host defense against extracellular organisms such as parasites. Eosinophils Allergic diseases are characterized by peripheral blood and tissue eosinophilia contains intracellular granules that are sources of inflammatory proteins Mast cells derived from CD 34 hematopoietic progenitor cells that arise from the bone marrow contains histamine, serine proteases and proteoglycans The most important mast cell-derived lipid mediators are the cyclo-oxygenase and lipoxygenase metabolites of Arachidonic Acid The major cyclo-oxygenase product of mast cells is Prostaglandin D2 The major lipoxygenase products are the sulfidopeptide leukotrienes: LTC4 and its peptidodytic derivatives LTD4 and LTE4. MECHANISMS OF ALLERGIC TISSUE INFLAMMATION Classification of Ig E mediated immune responses: 1. Early phase response 2. Late phase response 3. Chronic allergic disease 1. Early phase response immediate response after introduction of allergen into target organs Within 10 minutes after allergen exposure and resolving within 1-3 hrs. e.g. leakage of plasma proteins tissue swelling increased blood flow

Ex: itching, sneezing, wheezing, acute abdominal cramps in the skin, nose, lung, and GIT

2. Late Phase Response Can occur within hours of allergen exposure, reaching a maximum at 612 hrs. and resolving by 24 hours Clinically cutaneous LPRs characterized by edema, redness, and induration; sustained nasal blockage, wheezing 3. Chronic Allergic Disease Tissue inflammation can persist for days to years Risk factors: recurrent exposure to allergens and microbial agents Ex: Asthma remodelling involves thickening of the airway Atopic Dermatitis - lichenification DIAGNOSIS OF ALLERGENIC DISEASE Allergy History Risk of allergic disease in a child whose parent is allergic 50% Both parents 66% CHARACTERISTIC BEHAVIOR ALLERGIC CHILDREN: OFTEN SEEN IN

Allergic salute rubbing their nose upward with the palm of their hand because of nasal pruritus and rhinorrhea Nasal crease a horizontal skinfold over the bridge of the nose Allergic cluck is produced when the tongue is placed the roof of the mouth to form a seal and withdrawn rapidly in an effort to scratch the palate Aeroallergens pollens or fungal spores are prominent causes of allergic disease whose concentration in outdoor air fluctuates seasonally

PHYSICAL EXAMINATION Allergic Shiners blue gray to purple discoloration beneath the lower eyelids attributed to venous stasis Dennie lines Prominent symmetric skin folds that extend in an arc from the inner canthus beneath and parallel to the lower lid margin. Conjunctival Injection conjunctivitis and edema in allergic

CLINICAL MANIFESTATIONS 3 Stages I. Infantile stage Begins during the 4th-6th month erythematous, pruritic, weeping dermatitis in the cheeks which spread to the forehead and extensor surface of the arms and legs Cradle cap Disappears between 3rd-5th yr. of life Childhood stage 2-4 yrs. Pruritic, excoriated papules on the flexural surfaces of extremities and face Lichenification appear in the popliteal and antecubital fossa and ankles May disappear before 10 yrs. of age or continue to adulthood Mark of atopic dermatitis where there is whitish hue of the face Adult Stage Large areas of highly pruritic, confluent papules commonly involving the dorsal aspect of the hands, upper eyelids and flexural area of extremities

II.

External Ear eczematoid changes in Atopic dermatitis Nasal patency should be assessed, examined for septal deviation, turbinate hypertrophy, septal spurs, or nasal polyps Pale to purple nasal mucosa suggest allergic rhinitis. Lips reveal cheilitis caused by drying of the lips from continuous mouth breathing and repeated licking of the lips Post pharynx Presence of post nasal drip and post pharyngeal lymphoid hyperplasia Xerosis dry skin is the most common skin abnormality of allergic children Keratosis Pilaris Found on the extensor surfaces of the upper arms and thigh, characterized by roughness of the skin caused by keratin plugs lodged in the openings of hair follicles. Atopic Dermatitis a chronic, heritable, cutaneous inflammatory disease characterized by early age of onset of intense pruritus skin lesions maybe dry, easily irritated, weeping Progresses to excoriated and lichenified lesion on the flexural areas of the body in late children and adolescents Atopic eczema Genetic predisposition Relapsing course; increase Serum Ig E

III.

STIGMAS OF ATOPIC DERMATITIS Pruritus Characterized all phases of atopic dermatitis, intense during infancy Lichenification A dramatic increase in the visibility of the normal geometric skin markings pruritic on the sides of the neck and in the popliteal and antecubital fossa. Dennies line a prominent fold on the lower eyelid Atopic palms Increased fine palmar and digital creases and lines which are presumed to be a manifestation of dry skin Buffed nails Produced by chronic scratching and rubbing Abnormal Vascular reactions Studying of the skin of AD patients produces an initial erythematous line that is quickly

replaced by a whitish blanch white dermographism Dryness xerosis seen on the extensor surfaces of the extremities where there is also keratosis pilaris Deficient sweating Atopic Personality Reactive, active aggressive and somewhat hostile Housewife Eczema acute or chronic eczematous process occurring in the hand of young women Atopic foot Erythematous scaling ezcema involving dorsal and ventral aspect of the big toes TREATMENT: Avoidance of the triggers Food allergens: peanut, milk, eggs, and sea foods, inhalants (houses dust mites, mold spores) Extreme change in temperature Good hydration bathing or soaking the affected area for 15 mins. in tepid water Use of oatmeal to the bath water for soothing Moisturizer/creams Avoid soap and detergents, wool, silk, nylon and other synthetic fabrics physical irritants PHARMACOTHERAPY 1. Antihistamines prevent symptoms of IgEmediated allergic diseases, atropine like effect, asthma prophylaxis HI receptor antagonist useful in allergic disorders complete or block the action of histamine by reversible competitive antagonism at HI receptor H2 receptor antagonist ex. Cimetidine, ranitidinecan inhibit cell-mediated immune skin responses

mequitazine 36 hrs. passed BBB and placenta, metabolized in the liver SE: sedation, nausea and vomiting, suppression of parkinsonismlike syndrome

b. Newer Non classical HI anatagonists Terfenadine, astemizole lack of sedation and anti-cholinergic effects long acting, good compliance 2. Adrenergic Agents relax airway smooth muscle, inhibit release of chemical mediators from mast cells causing bronchoconstriction, increase mucociliary transport by ciliary activity Beta 2 adrenergic agents e.g. salbutamol, terbutaline, tolbuterol Epinephrine stimulate alpha B1 and B2 receptors given SQ 0.1 ml/kg of 1:1 dil, Rapid onset, counteracts asthmatic bronchospasm

3. Methylxanthine Theophylline- relaxes bronchial smooth muscle, stimulate ciliary motility, acts as CNS respiratory stimulant, improve diaphragmatic and other respiratory muscle contractility in the distressed asthmatic phosphodiesterase inhibition which increase the tissue levels of cyclic AMP inhibition of neural transmission at certain synapses SE: narrow range between clinically effected blood levels and levels producing side effects which include: anorexia, nausea, vomiting, heartburn, diarrhea, neurologic effects: headache, restlessness, insomnia, muscle spasm, seizure, cardiovascular effects: (palpitations, tachycardia, arrhythmia), allergy 4. Corticosteroid anti-inflammatory, potentiate the effects of beta adrenergic drugs decrease airway obstructions long term side effects: adrenal suppression leading to inhibition of linear growth and posterior subscapsular cataract long term use inhaled corticosteroid safe and effective e.g. Budesonide 5. Muscarinic Antagonist obviates the systemic atropine effects

2 Types of Histamines a. Classical rapidly absorbs after oral or parenteral administration relief appreciated within 15-30 min. e.g. meclizine- 12-24 hrs

competitively inhibit the effect of acetylcholine at muscarinic receptor causing relaxation of the airway smooth muscles and dec. secretion of mucus ex. Ipatropium bromide

Lung hyperinflation Increase Residual vol- & FRC Decrease VC, IC ERV Decrease Lung compliance Ventilation perfusion mismatch Clinical Presentation wheezing (high pitched or squeaking expiratory sound cough prolonged expiratory phase tachypnea and dyspnea w/ use of accessory muscles of respiration Hyperinflation of the chest Tachycardia Abdominal pain w/ vomiting Excessive sweating Fatigue and low grade fever from increase work of breathing Hunched-over sitting position Laboratory Chest X-ray hyperinflation w/ peribronchial thickening Allergy skin test or RAST : not all that wheezes is asthma

6. Cromolyn Sodium non-steroidal, inhaled anti-inflammatory drug, prevents both antibody-mediated mast cell degranulation and the transmembrane influx of Ca provoked by IgE antibody-antigen mediator-selective suppressive effect on antiinflammatory cells like macrophages, eosinophils, neutrophils and monocytes. 7. Ketotifen prophylaxis for asthma, a potent anti anaphylactic activity, inhibit release and effect of mediators, acts as Ca channel antagonists and optimizes the beta adrenergic responses. ASTHMA A chronic inflammatory disorder of the airways in which cells play a role, including mast cells and eosinophils Etiopathogenesis: Hyperresponsive of the airway muscles Activated by autonomic immunologic infectious - viral agents endocrine physiologic VIP (vasoactive intestinal peptide) smooth muscle relaxation Local hormonal factors (histamine and leukotrienes ) produces bronchoconstruction Increase Ig E Endocrine factors worsens asthma during pregnancy, menstruation and onset of menopause At puberty improves Thyrotoxicosis worsens the severity of asthma Emotional factors Abnormal behavioral characters affect childs self-confidence Pathophysiology (Triad): 1. Smooth muscle spasm with hypertrophy 2. Mucosal edema 3. Plugging with tenacious mucus, albumin, epithelial cells and eosinophilic leukocytes

DDx: Congenital malformations of the respiratory tract Cardiovascular and GI systems FB Croup, bronchiolotis, endobronchial TB, etc. Children over 5 y/o spirometry peak flow measurements Management: 1. Bronchodilator b2 agonists, theophylline, anticholinergic (ipatropium bromide) 2. Anti-inflammatory agents nedocromil sodium, sodium cromoglycate, corticosteroids)

STATUS ASTHMATICUS Severe acute asthma Progression of the attack unresponsive to the usual appropriate therapy Characteristics: Hx of frequent repeated attacks, exessive daily use of bronchodilator, corticosteroids Use of accessory muscles Pulsus paradoxus

Change in consciousness Cyanosis Pneumothorax and pneumonediastinum Hypoxemia w/ a PaCO2 less than 60mmHg Hypercapnea Metabolic acidosis FEV1 less than 20% predicted value EKG abnormalities like p Pulmonale vent. Strain, bundle branch blocks, axis deviation

Airborne allergens of large molecular weight and high protein content 2 TYPES 1. Seasonal rhinitis hay fever rare type in the Phil. classic picture of the dse in a predictable season of the year during pollenating season of plants occurs at any age but rarely before 4 or 5 yrs 2. Perennial allergic rhinitis most common type in the Phil. presents with sx the year round causative agents are usually allergens found continuosly in the environment house dust/mites, animal dander, molds

ADVERSE DRUG REACTION 1. Type I Drug Reaction Urticaria pruritus increase Ig E

2. Type II Cytotoxic reactions The antigenic determinants of the drug will interact with Ig G or Ig M or both antibodies will bind with the lymphocyte, leukocyte a platelets of the drug sensitive patients Activation is the destruction of the target cells Ex: quinidine induced hemolytic anemia 3. Type III toxic complex syndrome or Arthus phenomenon prototype of serum sickness Symptoms is due to tissue damage brought about by the action of proteolytic enzymes liberated from neutrophils Clinical features Urticaria with or w/o angioedema, erythematous, maculopapular rashes, erythema multiforme, arthralgia 4. Type IV- T cell-mediated Allergic reaction involves the lymphoid cells and not the hormonal antibodies Prototype: contact dermatitis (drug induced) - reaction to topical creams and lotion ALLERGIC RHINITIS Familial dse of unknown genetic transmission Type I allergic reaction Symptoms: rhinorrea, itching, congestion

Symptoms 1. Sneezing usually in the morning 2. Rhinorrhea thin, profuse and watery 3. Nasal obstruction or congestion edema of mucus membrane 4. Itching of nose, eyes, palate, pharynx, and ears Rabbit nose Allergic salute Allergic shiners dark circles under the eyes Mouth breathing Lid edema Periorbital swelling Diagnosis 1. Above signs and symptoms 2. Nasal smears (+) eosinophils 3. PBS eosinophils 4. Ig E 5. (+) skin test and RAST Differential Diagnosis Structural factors: 1. Choanal atresia 2. Deviated septum 3. Encephalocoele 4. Adenoidal hyperplasis 5. Nasal polyp 6. Congenital cyst

7. Foreign body unilateral foul smelling nasal discharge 8. Benign or malignant tumors Treatment Environmental control Allergy immunotherapy Avoidance of allergen Avoiding irritants o Drugs: H1 antihistamine Sympathomimetics (decongestants) Inhaled corticosteroid immunotherapy