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Allerg y& Immunology Board Review May 19, 2007

Allerg y& Immunology Board Review May 19, 2007

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Allerg y& Immunology Board Review May 19, 2007

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  1. Allergy& Immunology Board Review May 19, 2007 Anna Nowak-Wegrzyn, MD Mount Sinai School of Medicine Pediatric Allergy & Immunology New York, NY

  2. Pediatric Certification Exam • Allergy and related disorders: 4.5% [ID-5.5%, development 4.5%, neonatology 4.5%] • www.abp.org: General Pediatrics Exam Information: content outline • Allergic Rhinitis • Asthma • Atopic Dermatitis • Food Allergy • Anaphylaxis • Urticaria, angioedema • Drug Allergy • Hymenoptera Allergy • Diagnosis and treatment of allergic dz • Immunodeficiency disease

  3. Prevalence of Allergic Diseases • Atopic dermatitis • Up to 15-20% of children • Allergic rhinitis • 20% cumulative prevalence rate in the US [40% in young children] • Asthma • 5.4% in the US • Food allergy • Up to 8% of children less than 3 years of age • Up to 3-4% of adults Prevalence doubled in the past 20 years!

  4. Bonus! Genetics of Allergic Diseases • Complex genetic disease, in contrast to simple mendelian trait such as CF • Clear hereditary pattern (one parent atopic-risk in child 40%, both parents atopic-70% risk) • Asthma twin studies: 70-80% of susceptibility due to a genetic component; asthma in twins 4x higher if parents asthmatic • Susceptibility genes: ADAM33 in asthma, SPINK5 in AD

  5. Bonus! Factors Influencing the Development of Atopic Allergic Disease Factors favoring TH1 phenotype Factors favoring TH2 (allergic) phenotype • Developing countries • Presence of older siblings • Rural homes, livestock, pet (dog) ownership in childhood • Poor sanitation, high orofaecal burden • High helminth burden • Early exposure to day care • Tuberculosis, measles, or HAV infection • Widespread use of antibiotics • Western lifestyle • Urban environment • Diet • Sensitization to house dust mites and cockroaches • Good sanitation

  6. The Atopic March Food Allergy/Atopic Dermatitis Asthma/Allergic Rhinitis Prevalence -----Infancy---Toddler------Child--Teen-------Adulthood

  7. AD Prevalence • Prevalence: • Children: 10-20% • Adults: 1-3% • 85% present in the first year of life (but rarely under 2 months, 95% develop by age 4 years • Less severe by adolescence in 65%, but only 20% outgrow AD by age 11-13 years • Prevalence increased 2-3 fold during the past 3 decades in industrialized countries • Particularly common in Caucasians and Asians • Wide variations in prevalence between groups with similar genetic background imply critical role of environmental factors in determination of AD expression

  8. AD Diagnosis • No objective diagnostic test • Major criteria [Hanifin & Rajka Acta Derm Vener 1980; 92:44] • Pruritus • Chronic relapsing course • Typical distribution of eczema • Facial and extensor eczema in infants and children • Flexural eczema in adults

  9. AD diagnosis-minor criteria • Xerosis • Atypical vascular response (facial pallor, white dermatographism) • Perioral or periauricular lesions • Allergic shiners • Morgan-Dennie lines • Keratosis pilaris • Pityriasis alba • Palmar / plantar hyperlinearity • Anterior Capsular Cataracts • Keratoconus

  10. AD rash Acute • Pruritic erythematous papules • Serous exudation • Excoriation Chronic (skin remodelling) • Lichenification • Dry fibrotic papules • Hyperpigmentation

  11. Differential diagnosis of AD Bonus! • Seborrheic Dermatitis • Nummular eczema • Contact dermatitis (allergic, irritant) • Psoriasis • Ichtyoses • Dermatitis herpetiformis • Pemphigus foliaceus • GVHD • Dermatomyositis • Phenylketonuria • Zinc deficiency • Vitamin B 6 and niacin deficiency • SCID/Omen Syndrome • Wiskott-Aldrich Syndrome • Hyper IgE Syndrome • Agammaglobulinemia • Ataxia-telangectasia • Netherton’s Syndrome • Familial keratosis pilaris • HIV • Scabies • Cutaneous T cell lymphoma • Letterer-Siwe disease

  12. Skin Barrier Dysfunction Bonus! • Dry skin; increased trans-epidermal water loss • Increased allergen absorption, increased cutaneous hyper-reactivity • Reduced content of ceramides in non affected AD skin=primary epidermal defect • AD lesions: inflammation-induced skin damage

  13. Non-allergic AD triggers Bonus! • Irritants • Stress, anxiety • Low/high air humidity • Sweating Scratching Induce and sustain the inflammatory cascade initiated by the release of pro-inflammatory cytokines from atopic keratinocytes

  14. Atopic Dermatitis and Food Allergy • 35% of children with AD have skin symptoms provoked by food hypersensitivity (Eigenman et al, 1998) • 90% of food allergy caused by egg, cow’s milk, soy, wheat, peanut, and fish • Egg allergy is the single most common food allergy • 7 out of 10 children with AD and egg allergy develop respiratory allergy by age 5 years • Suspect food allergy in uncontrollable eczema that waxes and wanes without particular association with diet

  15. Atopic Dermatitis and Respiratory Allergy • Up to 80% have positive skin test to environmental allergens • Inhalation of dust mites causes AD flare within 24 hours • Exposure to pollen (tree, grass, ragweed) associated with seasonal AD flares • Skin contact with animal allergens, dust mites, pollens or molds causes eczema worsening or hives • Ingestion of foods cross-reactive with birch tree pollen in the birch season associated with AD • Degree of IgE sensitization to aeroallergens is directly associated with severity of AD

  16. Atopic Dermatitis and Allergic Airway Disease at Age 5 Years % children 50.2 28.1 12.2 AD+ / AD- in the first 3 months of life FH++ / FH- at least two atopic family members Bergmann et al, Clin Exp Allergy, 1998

  17. Microbes Bonus! • Most patients are colonized with Staphylococcus aureus • Th2 inflammation-IL-4-increased expression of fibronectin on collagen-increased S.aureus binding • AD skin is deficient in antimicrobial peptides (innate immunity) against bacteria, fungi, and viruses (HSV, molluscum, vaccinia, smallpox) • S.aureus toxins act as super-antigens that activate T cell and macrophages • Most AD patients make IgE antibodies against staphylococcal super-antigens that correlate with disease severity • S.aureus super-antigens induce corticosteroid resistance • Treatment with a combination of anti-staphylococcal antibiotics and topical corticosteroids result in greater clinical improvement that treatment with topical Cs alone

  18. AD - S. aureus Superinfection

  19. Eczema herpeticum

  20. Pruritus • Most important symptom • Major cause of morbidity • Interferes with normal sleep pattern

  21. Atopic Dermatitis Management Bonus! • Identify and avoid relevant food and environmental allergens-EDUCATION • Avoid irritants: wool and synthetic clothing, sweating, stress, harsh soap, laundry detergent • Lubrication • Antihistamines: hydroxyzine, cetirizine • Topical anti-inflammatory: steroids, tacrolimus • Systemic anti-inflammatory: steroids, cyclosporine • Phototherapy • Treatment of infections: S. aureus, HSV • National Eczema Association for Science and Education

  22. Atopic Dermatitis Lubrication Bonus! • Impaired skin barrier as a result of allergic inflammation - increased water loss • Daily soaking baths • Application of moisturizer within 3 minutes

  23. Food Allergy • Non-toxic, immune-mediated adverse reaction to food • Up to 6-8% of children • 2.5% of infants <1 year allergic to cow’s milk, 85% outgrow by age 3 (Host and Halken, 1994) • 1.3% allergic to egg (Nickel et al, 1997) • 0.5% allergic to peanut in UK and US (Tariq et al, 1996; Sicherer et al, 1999)-recent studies:1% • 35% of children with AD have skin symptoms provoked by food hypersensitivity (Eigenman et al, 1998) • 6% of asthmatic children have food-induced wheezing ( Novembre et al, 1988)

  24. Adverse Food Reactions Toxic Non-Toxic Food poisoning Non-Immune Mediated Immune-Mediated Lactase deficiency IgE-Mediated Non-IgE-Mediated Enterocolitis Proctocolitis Eosinophilic gastroenteritis Eczema Urticaria Anaphylaxis

  25. Food Allergens Children Adults • Milk • Egg • Peanut • Soybean • Wheat • Tree nuts • Fish • Shellfish • Peanut • Tree nuts • Fish • Shellfish

  26. Food Allergy Syndromes IgE mediation Mixed Mechanisms Non-IgE Mediation Immediate GI Hypersensitivity Allergic Eosinophilic Gastroenteritis Food Protein Induced Enterocolitis, Proctocolitis Gastrointestinal Oral Allergy Syndrome Oropharyngeal Acute Urticaria & Angioedema Atopic Dermatitis Dermatitis Herpetiformis Cutaneous Acute Bronchospasm* Asthma* Food-Induced Pulmonary Hemosiderosis Respiratory Common Uncommon * Risk factor for severe anaphylaxis

  27. Symptoms of Acute Food Allergy

  28. Cutaneous Manifestations of Food Allergy

  29. Risk Factors for Fatal Food Anaphylaxis • Peanut and tree nut allergy • Asthma • Delayed administration of epinephrine • Bock, Munoz-Furlong, Sampson, et al, 2001

  30. Treatment of Food Anaphylaxis Bonus! • Clear emergency treatment plan for the patient • Prompt recognition of symptoms • Oral antihistamines • Benadryl syrup, 1-1.5 mg/kg/dose • Parenteral epinephrine • Self-injectable device • EpiPen Jr / Twinject Jr. 0.15 mg, under 55-66 lbs • Epi Pen / Twinject 0.3 mg, over 55-66 lbs • Follow up in the ED or call 911

  31. Clinical Pearl: FA & Immunizations ! • Children with egg allergy may receive MMR as per routine protocol, no increased risk for allergic reactions • Influenza vaccine contains egg protein and may cause allergic reactions in egg allergic children • Children allergic to gelatin may react to gelatin stabilizer in vaccines, i.e. MMR

  32. Asthma-Definition • Asthma is a chronic inflammatory disorder: • Airway inflammation underlies the airway hyper-responsiveness to asthma triggers. • The airway hyper-responsiveness leads to airway obstruction that is usually fully reversible. • Obstruction leads to the classic symptoms of asthma: cough, wheeze, and dyspnea. National Asthma Education and Prevention Program. Highlights of theExpert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD., May 1997. NIH Publication No. 97-4051A.

  33. Bonus!

  34. Onset of Symptoms in Children With Asthma 20% 30% 1-2years <1 year 20% 2-3 years 30% >3 years McNicol and Williams. BMJ 1973;4:7-11. Wainwright et al. Med J Aust 1997;167:218-222.

  35. Asthma-Natural History • The natural history and prognosis of pediatric asthma is incompletely understood. • Most children “don’t grow out of asthma”1. Instead, the “loss” of symptoms may actually be related simply to growth of the lungs and not due to a change of airway hyper-responsiveness. The “loss” of symptoms may thus represent a period of time when the disease goes through a silent, asymptomatic period only to recur later in life2. • 1Martinez, FD. In: Barnes PJ, Leff AR, Grunstein MM, Woolcock AJ., eds. Asthma. Philadelphia PA: Lippincott - Raven; 1997:121-128. • 2 Weiss ST, Environmental risk factors in childhood asthma. Clin Exp Allergy. 1998;28(suppl 5):29-34.

  36. Bonus! Predictors of Persistent Asthma • Family history (more important on the maternal than on the paternal side) • Atopy: elevated IgE in the 1st year of life, peripheral blood eosinophilia >4% (2-3 years of age) and other atopic diseases: AD, AR, FA • Viral infections: RSV, parainfluenza, severe bronchiolitis • Male gender • Smoking: passive or active; pre – or postnatal exposures • Severity of asthma in childhood • Ehrlich et al. Risk Factors for childhood asthma and wheezing. Am J Resp Crit Care Med. 1996;154:681-688. • Martinez FD et al. Asthma and wheezing in the first 6 years of life. N Engl J Med 332:133-8, 1995. • von Mutius E and Martinez FD. In: Murphy S and Kelly HW., eds. Pediatric Asthma: Marcel Dekkar; 1999:17-25.

  37. Clinical Pearl ! • The most common CAUSE of wheezing in young children is viral respiratory infection BUT • The strongest predictor for wheezing that develops into asthma is ATOPY

  38. Role of Allergens in Asthma • Atopy is one of the strongest asthma risk factors • Indoor allergens • House dust mites • Domestic pets • Cockroaches • Molds • Outdoor allergens • Alternaria - a risk factor for childhood asthma (Peat et al. 1993, 1994) • Ragweed (Creticos et al. 1996) and grass (Reid et al. 1986) associated with seasonal asthma exacerbations

  39. Potential Triggers of Asthma • The two components of asthma: • Inducers • Allergens • Viral infections • Occupational • Provokers • Exercise • Irritants • Emotions • Aspirin

  40. NHLBI Guidelines for Diagnosis and Management of Asthma 1997& 2002 • Exposure to allergens to which patients are sensitive has been shown to increase asthma symptoms and precipitate asthma exacerbations • For at least those patients with persistent asthma • Identify allergen exposure • Use the patient’s history to assess sensitivity to seasonal allergens • Use skin testing or in vitro testing to assess sensitivity to perennial allergens • Assess the significance of positive tests in context of the patient’s medical history

  41. When Is It Asthma? ! • Repeated cough, wheeze, chest tightness • Repeated dx of RAD, allergic bronchitis, or wheezy bronchitis • Symptoms worsened by viral infection, smoke, allergens, exercise, weather • Symptoms occur / worsen at night • Reversible flow limitation ( increase in FEV1 by 12% post-bronchodilator) • Wheezing may or may not be present • Persistent cough may be the only symptom

  42. Bonus! Asthma Severity* • Intermittent • Daytime sxs < 2x / week • Asymptomatic and normal PEF between exacerbations • Exacerbations brief (few days), varying intensity • Nighttime sxs < 2x / month • Mild persistent • Daytime sxs >2x / week but <1x / day • Exacerbations may affect activity • Nighttime sxs 3-4 x / month • Moderate persistent • Daytime sxs daily • Daily use of inhaled beta2-agonist • Exacerbations affect activity; > 2x / week, may last days • Nighttime sxs 5-9 x / month • Severe persistent • Continual daily sxs, nighttime sxs >10 x / month • Limited physical activity • Frequent exacerbations *Assessment before starting therapy; on therapy need to adjust for meds by stepping up severity

  43. Bonus! Goals of Asthma Treatment • Prevent chronic and troublesome symptoms • Normal lung function ( FEV1 / PEF >80% of predicted/personal best) • Normal activity / exercise • Prevent recurrent exacerbations • Eliminate/minimize ED visits and hospitalizations • Optimal pharmacotherapy with minimal or no adverse effects; minimal use <1x / day of short-acting beta2-agonist

  44. Principles of Asthma Therapy • Avoidance of allergens and environmental triggers: tobacco smoke, fumes, irritants • Pharmacologic therapy • Immunotherapy A. Specific allergen IT (allergy shots) B. Anti-IgE antibody

  45. Severity-based Therapy for Asthma Bonus!

  46. Bonus! Acute Asthma Episode • Acute inset of symptoms, PEF<80% • Short-acting beta2 agonist inhaler/nebulized tx up to 3x in one hour • If PEF>80% or symptoms resolved completely: add or double the dose of ICS for 7-10 days and continue beta2 agonist every 2-4 hours for 1-2 days PRN, contact PCP within 48 hours • If PEF 50-80% or persistent symptoms: beta2 agonist q 2-4 hours and add oral steroid 2mg/kg/day x 5 days; contact PCP within 24 hours • If PEF<50 or severe symptoms: Ed or call 911, repeat treatment while waiting, start oral steroid (if available)

  47. Allergic Rhinitis • Prevalence 3-19% • Seasonal allergic rhinitis 10% • Perennial allergic rhinitis 10-20% • In the US 20-40 million people affected • Physician-diagnosed AR in 42% of 6-year-old children (Wright et al, 1994) • The most common allergic disease in children • Symptoms develop by 20 years in 80%; 20% by age 2-3 years, 40% by age 6 years, and 30% during adolescence

  48. Allergic Rhinitis: Symptoms • Sneezing • Itching • Rhinorrhea • Nasal congestion • Postnasal drip • Cough • Halithosis • Nasal speech • Itchy, runny eyes

  49. Allergic Rhinitis: Physical Findings