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Allergy

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Title: Allergy


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
Genetics of Allergic Diseases
Bonus!
  • 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
Factors Influencing the Development of Atopic
Allergic Disease
Bonus!
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-------Adul
thood
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 9244
  • 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
  • Nethertons 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
    skinprimary 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, cows 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 lt1 year allergic to cows 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
    studies1
  • 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
Immune-Mediated
Non-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
1-2 years
lt1 year
20
2-3 years
30
gt3 years
McNicol and Williams. BMJ 197347-11.
Wainwright et al. Med J Aust 1997167218-222.
35
Asthma-Natural History
  • The natural history and prognosis of pediatric
    asthma is incompletely understood.
  • Most children dont grow out of asthma1.
    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 1997121-128.
  • 2 Weiss ST, Environmental risk factors in
    childhood asthma. Clin Exp Allergy. 199828(suppl
    5)29-34.

36
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37
Predictors of Persistent Asthma
Bonus!
  • Family history (more important on the maternal
    than on the paternal side)
  • Atopy elevated IgE in the 1st year of life,
    peripheral blood eosinophilia gt4 (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.
    1996154681-688.
  • Martinez FD et al. Asthma and wheezing in the
    first 6 years of life. N Engl J Med 332133-8,
    1995.
  • von Mutius E and Martinez FD. In Murphy S and
    Kelly HW., eds. Pediatric Asthma Marcel Dekkar
    199917-25.

38
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

39
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
40
Potential Triggers of Asthma
  • The two components of asthma
  • Inducers
  • Allergens
  • Viral infections
  • Occupational
  • Provokers
  • Exercise
  • Irritants
  • Emotions
  • Aspirin

41
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 patients 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 patients medical history

42
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

43
Asthma Severity
Bonus!
  • Intermittent
  • Daytime sxs lt 2x / week
  • Asymptomatic and normal PEF between exacerbations
  • Exacerbations brief (few days), varying intensity
  • Nighttime sxs lt 2x / month
  • Mild persistent
  • Daytime sxs gt2x / week but lt1x / 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 gt 2x / week, may
    last days
  • Nighttime sxs 5-9 x / month
  • Severe persistent
  • Continual daily sxs, nighttime sxs gt10 x / month
  • Limited physical activity
  • Frequent exacerbations

Assessment before starting therapy on therapy
need to adjust for meds by stepping up severity
44
Goals of Asthma Treatment
Bonus!
  • Prevent chronic and troublesome symptoms
  • Normal lung function ( FEV1 / PEF gt80 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 lt1x / day of
    short-acting beta2-agonist

45
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

46
Severity-based Therapy for Asthma
Bonus!
Severity Preferred Alternative PRN
Intermittent Mild persistent Moderate persistent Severe persistent No daily meds Low-dose ICS Low-medium dose ICS AND long-acting beta2-agonist High dose ICS AND long-acting beta2-agonist N/A Cromolyn, leukotriene modifier, nedocromil, OR sustained release theophylline Increased ICS in medium dose range , OR add leukotriene modifier or theophylline Oral CS for severe exacerbations
47
Acute Asthma Episode
Bonus!
  • Acute inset of symptoms, PEFlt80
  • Short-acting beta2 agonist inhaler/nebulized tx
    up to 3x in one hour
  • If PEFgt80 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 PEFlt50 or severe symptoms Ed or call 911,
    repeat treatment while waiting, start oral
    steroid (if available)

48
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

49
Allergic Rhinitis Symptoms
  • Sneezing
  • Itching
  • Rhinorrhea
  • Nasal congestion
  • Postnasal drip
  • Cough
  • Halithosis
  • Nasal speech
  • Itchy, runny eyes

50
Allergic Rhinitis Physical Findings
51
United Airway Disease
Bonus!
  • 58 of patients with SAR have asthma (Mullarkey
    et al, 1980)
  • 32 of children with AR have asthma as opposed to
    8 of children with rhinitis and negative skin
    tests (Wright et al, 1994)
  • Long term follow up of college students with AR
    3-fold greater risk of developing de novo asthma
    as compared to subjects without AR (Settipane et
    al, 1994)

52
Wright AL, et al. Pediatrics. 1994
Dec94(6)895-901.
53
Year-Round Symptoms
  • Indoor pets
  • Moisture or dampness in any room
  • Visible mold in any part of the house
  • Cockroaches and or mice in the house in the past
    month
  • Assume exposure to dust mites unless patient
    lives in a semi-arid region

54
Seasonal Symptoms
  • Early spring - trees (oak, maple)
  • Late spring - grasses (timothy)
  • Late summer to autumn - weeds (ragweed)
  • Summer and fall - molds (Alternaria, Cladosporium)

55
Dust Mite Allergy
  • Dermatophagoides farinae, Dermatophagoides
    pteronyssimus - major allergens
  • Exposure to dust mite allergens can induce
    perennial asthma and AR
  • Mite bodies and feces are the principal source of
    the allergens

56
House Dust Mite Control Improves Asthma
Murray and Fergusson, 1983
57
First Line Dust
MiteControls
Bonus!
  • Pillow cover (lt10 mcm pore, fine weave, or
    vapor-permeable)
  • Mattress vapor permeable or plastic cover
  • Box spring vinyl or plastic cover
  • Weekly bedding washing in hot (130 F) water
  • Removal of stuffed animals and toys from bed
  • Weekly vaccum cleaning
  • Double thickness bags or high-efficiency
    particulate air filter on an air outlet

58
Animal Allergy
  • Important allergens from cats, dogs, rats, mice,
    horses, cows
  • Sensitivity to cat and dog in 22 to 67 of
    asthmatics
  • Cat sensitization even in the absence of obvious
    exposure
  • Effects of early life cat exposure???
  • Cat and rat challenge studies - acute allergen
    exposure induces asthma symptoms and pulmonary
    changes
  • Less well characterized role of animal allergens
    in chronic asthma

59
Cat Allergen
  • Cat hair

60
Environmental Control of Animal
Allergens
  • Remove cat from home
  • Clinical benefit may be delayed for 4-6 months
  • Extensive cleaning
  • New bedding or impermeable encasements (cat
    allergen persists in mattresses for year)

61
What Works if Pets Stay?
Bonus!
  • Keep animals out of patients bedroom
  • Use HEPA or electrostatic air cleaners in bedroom
    and living room
  • Remove carpets and other allergen reservoirs
  • Use mattress and pillow covers

62
Cockroach Allergy
  • Up to 60 of inner city children with asthma
    sensitized to cockroach
  • Highest allergen levels in the kitchen and
    bathroom
  • Major allergens in the digestive secretions and
    on body parts of cockroaches
  • Limited data on health effects of cockroach
    controls
  • Mouse urinary protein is also an important
    allergen for asthmatic children living in the
    inner city

63
Cockroach Allergy and Asthma Hospitalizations in
the Inner City Children
p0.001
Group 1 No cockroach allergy, low exposure Group
2 No cockroach allergy, high exposure Group 3
Cockroach allergy, low exposure Group 4 Cockroach
allergy, high exposure
Rosenstreich et al, NEJM, 1997
64
Common Cockroaches Found in Homes
  • American
  • Oriental
  • German
  • Brown-banded

65
Cockroach Controls
Bonus!
  • Integrated pest management
  • Professional pesticide extermination
  • Vacuuming and wet-washing of the home
  • Behavioral changes to prevent re-infestation
  • place trash outside the home nightly or daily
  • store food in sealed plastic containers
  • wash dishes daily
  • seal cracks and other portals of entry
  • remove sources of standing water (refrigerator
    drip pans and leaking plumbing)

66
Fungal Allergy
  • Sensitization to Alternaria - risk factor for
    development of asthma, increased severity of
    asthma, and fatal asthma
  • Indoor molds Penicillium and Aspergillus
  • Outdoor molds Alternaria and Cladosporium
  • Fungi grow in mycelium and reproduce through
    spores, which become airborne

67
Indoor Mold Controls
Bonus!
  • Prevent spore infiltration form the outside
  • door and window closing
  • air conditioning
  • Prevent indoor mold growth
  • control moisture by dehumidification and seal
    water leaks
  • clean and remove contaminated materials with
    fungicides (chlorine bleach with detergent or
    quarternary amine preparations)
  • use high-efficiency air filters
  • maintain heating ventilation
  • use personal protective equipment (particle mask)
    when cleaning contaminated materials

68
Urticaria and Angioedema
  • Transient pruritic rash (welts or hives)
  • Acute
  • 10-20 of general population
  • Drugs, food, viral infection, insect bites
  • Chronic
  • Over 6 weeks
  • Difficult to identify the trigger,
  • Mostly post-viral
  • Evaluation
  • History and physical examination
  • Allergy testing if indicated
  • Skin biopsy if lesions persist in the same
    location gt24 hrs
  • Other CBC, ESR, Stool OP, TFTs, etc.

69
Urticaria
Classic
Cholinergic
Cold - induced
Solar
Dermatographism
70
Urticaria -Treatment
  • Remove the offending agent
  • Antihistamines
  • Avoid ASA or NSAIDs
  • Steroids
  • Referral

71
Anaphylaxis
  • Systemic IgE-mediated immediate hypersensitivity
    reaction
  • Non-IgE-mediated Anaphylactoid reaction
  • Release of histamine and other mediators from
    mast cells and / or basophils
  • Biphasic course early and late symptoms
  • Skin symptoms may be absent in up to 10-15 of
    most severe anaphylaxis

72
Etiology of Anaphylaxis
  • In hospital medications (ASA and NSAIDs,
    antibiotics, radiocontrast media, induction
    anesthetic agents, insulin, protamine,
    progesterone), latex, foods
  • Outside hospital
  • Yocum et al, 1999 36 foods, 17 medications,
    15 insect stings
  • Pumphrey et al, 1996 foods (peanut and tree
    nuts) major cause in north-west England
  • Novembre et al, 1998 foods responsible for 50
    of anaphylaxis in children treated in the ER

73
Treatment of Anaphylaxis
  • Recognize the symptom pattern
  • Measure serum tryptase (marker of mast cell
    degranulation) elevated 30 min up to 18 hours
  • I. M. epinephrine 11000, 0.01 mL/kg (0.3-0.5 ml)
  • I. V. antihistamine (H1, H2 blockers), steroids,
    fluids, oxygen
  • Observation gt 4 hours
  • Refer for allergy evaluation to identify the
    trigger
  • Clear emergency treatment plan
  • Rx self-injectable epinephrine device

74
Drug Allergy
  • IgE-mediated
  • Hives, anaphylaxis
  • Non-IgE-mediated
  • Maculopapular rash
  • Serum sickness
  • Stevens-Johnson
  • Anaphylactoid direct release of histamine
  • Radiocontrast media
  • Vancomycin
  • Opiates

75
Drug Allergy - Treatment
  • Stop the drug
  • Use alternatives from a different class
  • Skin testing to penicillin
  • Desensitization (gradual administration)
  • not indicated in SJS, TEN, serum sickness,
    reactions to anti-convulsants
  • Treat through mild reaction

76
Radiocontrast Media
  • Urticaria, angioedema, laryngo/bronchospasm,
    shock, death
  • Incidence 1.7 of IVP
  • Recurrence 16 on subsequent administration
  • ? risk atopy, older age, CHD, use of ? -
    blockers, asthma
  • Allergy to seafood and sensitivity to iodine are
    not risk factors
  • ? recurrence with newer, non-ionic, lower osmolar
    RCM
  • Pre - medication with prednisone 50 mg po 13, 7,
    and 1 hours prior to procedure, diphenhydramine
    50 mg po 1 hour prior ? ? risk by 5-10x
  • Consider pre - medication for high risk patients
    without h/o prior reactions strongly atopic,
    extensive cardiovascular disease

77
Insect Sting Allergy
  • Most common offenders Yellow Jacket, Hornets,
    Wasp, Honeybee, Bumblebee, and Fire Ant
  • Degrees of severity
  • Local or large local
  • Toxic
  • Delayed
  • Systemic
  • Systemic reaction Rx self-injectable epinephrine
    device and refer for allergy evaluation
  • Skin testing and serum venom - IgE
  • Venom IT reduces risk from gt50 to lt2
  • Under 16 years of age generalized urticaria is
    not associated with increased risk for ANA upon
    subsequent stings, not an indication for VIT

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Allergy Evaluation
  • History and physical exam
  • Prick skin testing
  • Serum allergen-specific IgE
  • Challenge

79
Allergy Diagnosis
Bonus!
  • Skin test
  • Less expensive
  • Greater sensitivity
  • Wide allergen selection
  • Immediate results (10-15 minutes)
  • Serum Immunoassay
  • No patient risk
  • Convenience
  • Not affected by antihistamines
  • Quantitative results
  • Preferable to skin testing in
  • Dermatographism
  • Extensive eczema
  • Uncooperative patient

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Bonus!
Food Allergen-Specific IgE levels (kU/L) in the
Diagnosis of Food Allergy
Sampson HA, JACI, 2001
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Atopy Markers and Risk Factors
  • Family history, mothergtfather
  • Increased IgE in cord blood and in infancy
  • Male gender
  • Brief or no breast-feeding, early introduction of
    solid foods
  • Early allergen exposure (foods, mites, pets,
    pollens-season of birth)
  • Passive smoking in utero and post-natal
  • RSV infection
  • Tightly ventilated houses, household dampness

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Allergy Prevention
Bonus!
  • Avoidance of highly allergenic foods in pregnancy
    and during breast-feeding
  • Prolonged breast-feeding
  • Wean/supplement with extensively hydrolyzed
    hypoallergenic protein hydrolysate
  • Delayed introduction of solid foods
  • Cows milk / dairy 6-12 months
  • Egg 12-24 months
  • Peanut, tree nuts, fish, shellfish gt36 months
  • Aeroallergen avoidance
  • Dust mites
  • Animals

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Allergen Immunotherapy
  • Subcutaneous injections of specific allergen in
    gradually increasing doses environmental
    allergens, insect venoms
  • Generally indicated for subjects who dont
    respond well to pharmacotherapy
  • Allergen avoidance always recommended
  • Useful for AR, asthma, venom allergy generally
    not indicated for AD and contraindicated in food
    allergy

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Clinical Features of Immunodeficiency
  • Increased susceptibility to infection
  • Chronic / recurrent infections without other
    explanations
  • Infections with organisms of low virulence
    (P.carinii, invasive fungal infections, vaccine
    Polio, BCG infection after vaccination)
  • Severe infections pneumonia with empyema,
    bacterial meningitis, arthritis, sepsis,
    mastoiditis
  • Autoimmune or inflammatory disease
  • Target cells hemolytic anemia, ITP, thyroiditis
  • Target tissues RA, vasculitis, SLE
  • Syndrome complexes

85
ID Syndromes with Increased Sinopulmonary
Infections
  • Ataxia teleangiectasia
  • Ataxia, telangiectasia, variable B and T
    lymphocyte dysfunction, dysfunctional swallow
    with pulmonary aspiration
  • DiGeorge
  • CHD, hypoparathyroidism, abnormal facies thymic
    hypoplasia or aplasia cleft palate, dysfunction
    of soft palate
  • Dysmotile cilia
  • Situs inversus Kartageners syndrome, male
    infertility, ectopic pregnancy, upper and lower
    resp. tract infections immotile cilia
  • Hyper-IgE
  • Coarse facies, exczematoid rash, retained primary
    teeth, bone fractures, pneumonia elevated serum
    IgE, eosinophilia
  • Wiskott-Aldrich
  • Thrombocytopenia, eczema, variable B and T
    lymphocyte dysfucntion

86
Patterns of Illnesses Associated with Primary ID
  • Antibody sinopulmonary inf., GI (enterovirus,
    Giardia) autoimmune dz
  • T-cell immunity pneumonia (bacteria, P. carinii,
    virus), GI viral inf., skin/mucous membranes
    (fungi)
  • Complement sepsis, meningitis( Strep,
    Pneumococcus, Neisseria) autoimmune dz (SLE,
    gromeluronephritis)
  • Phagocytosis skin, RES, abscesses
    (Staphylococcus, enteric bacteria, fungi,
    mycobacteria)

87
Antibody Deficiency
  • X-linked agammaglobulinemia
  • Only boys, infections start by 9-18 months
  • Absence of tonsils and lymph nodes on PE
  • Pneumonia, chronic enteroviral meningitis,
    vaccine-Polio, mycoplasma/ureaplasma arthritis
  • Common variable immunodeficiency
  • Onset 1st and 3rd decades of life, both sexes
  • Sinopulmonary infections, asthma, chronic
    rhinitis, IBD, autoimmnue disorders (pernicious
    anemia, thrombocytopenia) 1.4-7 develop B cell
    lymphoma
  • IgA deficiency
  • Prevalence 1700 whites mostly asymptomatic
  • May be associated with chronic bacterial
    sinusitis, atopy, autoimmne dz (Crohns, IBD,
    SLE)
  • IgG subclass deficiency
  • IgG2 and IgG4
  • Controversy re if clinically relevant may be
    associated with recurrent sinopulmonary
    infections
  • Transient hypogammaglobulinemia of infancy
  • IgG transported via placenta, nadir 3-9 months
    postnatal life
  • Begins in infancy, resolves spont. By 36-48
    months of age
  • Most asymptomatic but may present with recurrent
    infections
  • Some children have food allergy
  • Typically normal responses to vaccines ( IgG to
    tetanus, diphtheria)

88
Severe Combined Immunodeficiency (SCID)
  • Positive family hx ( X-linked, parental
    consanguinity)
  • Presentation early in life first 4-6 months of
    age
  • Severe respiratory infections (interstitial
    pneumonia)
  • Protracted diarrhea
  • Failure to thrive
  • Persistent oral thrush
  • Skin rash, erythrodermia
  • Laboratory findings
  • Lymphopenia (ALClt2000/µl)
  • Reduced CD3T lymphocytes (lt1500/µl)
  • Very low or undetectable levels of serum
    immunoglobulins (although may be initially normal
    due to transplacental passage of maternal IgG)
  • Very low to absent in vitro proliferative
    responses to mitogens
  • Treatment medical emergency! aggressive tx of
    infections, PCP prophylaxis, IVIG, isolation,
    irradiate blood products, BMT!!!

89
White Blood Cell Defects
  • Defective oxidative burst Chronic granulomatous
    disease
  • May be X-linked or AR
  • Recurrent life threatening infections by catalase
    positive bacteria (Staph aureus, Nocardia,
    Salmonella, Serratia, Burkholderia cepacia) and
    fungi (Aspergillus, Candida) and exuberant
    granuloma formation (liver, gut, GU), abscesses,
    suppurative adenitis, osteomyelitis
  • Peripheral blood neutrophilia during the
    infection
  • Aspergillus pneumonia-major cause for mortality
  • Tx prophylaxis with Bactrim, itraconazole and
    IFN-?
  • Neutropenias
  • Defective granule formation and content
    Chediak-Higashi syndrome
  • AR, oculocutaneous albinism, pyogenic infections,
    neurologic abnormalities, late onset lymphoma
  • Leukocyte adhesion deficiency (types 1-4)
  • LAD 1 AR, deficiency of CD18 and as result of
    CD11 a-c
  • Defective neutrophil chemotaxis and tight
    adherence
  • Delayed umbilical cord separation, omphalitis,
    severe destructive gingivitis and periodontitis,
    recurrent infections of skin, upper/lower
    airways, bowel and perirectal area (necrosis,
    ulceration) S. aureus, gram-negative bacilli
  • Peripheral blood leukocytosis gt15,000 /µl
    (baseline), eosinophilia,

90
Differential Diagnosis
  • Allergy
  • Cystic fibrosis
  • Ciliary dysmotility due to recurrent infections
  • Localized abnormalities of anatomy or physiology
    (i.e., cleft palate, neurological impairment)
  • Secondary immunodeficiency HIV,
    leukemia/lymphomas, chemotherapy
  • Environmental factors
  • Day care attendance, sick older siblings
  • Exposure to irritants tobacco smoke, fumes, etc

91
Screening Tests
  • Antibody
  • Serum IgG, IgA, IgM
  • IgG to immunizations tetanus, diphtheria, Strep.
    pneumoniae
  • T-cell immunity
  • Lymphocyte count ( lt2000/ul)
  • T cell enumeration (CD3, CD4, CD8)
  • HIV serology
  • Complement
  • CH50
  • Phagocytosis
  • Neutrophil count
  • Nitroblue tetrazolium test or other tests for
    oxidative burst
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