Allergy& Immunology Board Review May 19, 2007

Anna Nowak-Wegrzyn, MD

Mount Sinai School of Medicine

Pediatric Allergy & Immunology

New York, NY

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

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!

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

Bonus!

Factors Influencing the Development of Atopic Allergic Disease

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

Factors favoring TH1 phenotype

Factors favoring TH2 (allergic) phenotype

Bonus!

The Atopic March

-----Infancy---Toddler------Child--Teen-------Adulthood-----Infancy---Toddler------Child--Teen-------Adulthood

Pre

vale

nce

Pre

vale

nce

Food Allergy/Atopic DermatitisAsthma/Allergic Rhinitis

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

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

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

AD rash Acute• Pruritic erythematous

papules • Serous exudation• Excoriation

Chronic (skin remodelling)• Lichenification• Dry fibrotic papules• Hyperpigmentation

Differential diagnosis of AD• 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

• 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

Bonus!

Skin Barrier Dysfunction

• 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

Bonus!

Non-allergic AD triggers

• 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

Bonus!

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

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

Atopic Dermatitis and Allergic Airway Disease at Age 5 Years

0

10

20

30

40

50

60

FH-/AD- AD+ FH++/AD+

AD+ / AD- in the first 3 months of life

FH++ / FH- at least two atopic family members

Bergmann et al, Clin Exp Allergy, 1998

12.2

28.1

50.2

% children

Microbes• 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

Bonus!

AD - S. aureus Superinfection

Eczema herpeticum

Pruritus

• Most important symptom

• Major cause of morbidity

• Interferes with normal sleep pattern

Atopic Dermatitis Management

• 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

Bonus!

Atopic Dermatitis Lubrication

• Impaired skin barrier as a result of allergic inflammation - increased water loss

• Daily soaking baths• Application of moisturizer within 3 minutes

Bonus!

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)

Adverse Food ReactionsToxic Non-Toxic

Food poisoning

Immune-MediatedNon-Immune Mediated

IgE-Mediated Non-IgE-Mediated

Lactase deficiency

Eczema

Urticaria

Anaphylaxis

Enterocolitis

Proctocolitis

Eosinophilic gastroenteritis

Food Allergens

Children AdultsMilkEggPeanutSoybeanWheatTree nutsFishShellfish

PeanutTree nutsFishShellfish

Food Allergy SyndromesIgE mediation Mixed Mechanisms Non-IgE Mediation

Gastrointestinal

Cutaneous

Oropharyngeal

Respiratory

Common Uncommon

Immediate GIHypersensitivity

Oral Allergy Syndrome

Acute Urticaria &Angioedema

Acute Bronchospasm*

Allergic Eosinophilic Gastroenteritis

Atopic Dermatitis

Asthma*

Food Protein Induced Enterocolitis, Proctocolitis

Dermatitis Herpetiformis

Food-Induced Pulmonary Hemosiderosis

* Risk factor for severe anaphylaxis

Symptoms of Acute Food Allergy

Cutaneous Manifestations of Food Allergy

Risk Factors for Fatal Food Anaphylaxis

• Peanut and tree nut allergy

• Asthma

• Delayed administration of epinephrine– Bock, Munoz-Furlong, Sampson, et al, 2001

Treatment of Food Anaphylaxis

• 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

Bonus!

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

!

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.

Bonus!

Onset of Symptoms in Children With Asthma

McNicol and Williams. BMJ 1973;4:7-11. Wainwright et al. Med J Aust 1997;167:218-222.

30%

20% 30%

20%

1-2 years

>3 years

<1 year

2-3 years

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.

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.

Bonus!

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

!

Role of Allergens in Asthma Role of Allergens in Asthma

Atopy is one of the strongest asthma risk factorsIndoor allergens

House dust mitesDomestic petsCockroachesMolds

Outdoor allergensAlternaria - 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

Potential Triggers of Asthma

• The two components of asthma:– InducersInducers

• Allergens• Viral infections• Occupational

– ProvokersProvokers• Exercise• Irritants• Emotions• Aspirin

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

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

!

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

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

Bonus!

Principles of Asthma Therapy

I. Avoidance of allergens and environmental triggers: tobacco smoke, fumes, irritants

II. Pharmacologic therapy

III. ImmunotherapyA. Specific allergen IT (allergy shots)

B. Anti-IgE antibody

Severity-based Therapy for Asthma

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

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)

Bonus!

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

Allergic Rhinitis: Symptoms

• Sneezing• Itching • Rhinorrhea• Nasal congestion• Postnasal drip• Cough• Halithosis• Nasal speech• Itchy, runny eyes

Allergic Rhinitis: Physical Findings

United Airway Disease

• 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)

Bonus!

Early Allergic Rhinitis as RiskEarly Allergic Rhinitis as RiskFactor for AsthmaFactor for Asthma

0

10

20

30

40

50

60

70

80

90

allergic allergic non-allergicRhinitis

Skin prick test POS NEG undetermined

Allergic rhinitis symptoms

Asthmasymptoms

Documented asthma

Ch

ild

ren

wit

h s

ymp

tom

s, %

Wright AL, et al. Pediatrics. 1994 Dec;94(6)895-901.

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

Seasonal Symptoms

• Early spring - trees (oak, maple)

• Late spring - grasses (timothy)

• Late summer to autumn - weeds (ragweed)

• Summer and fall - molds (Alternaria, Cladosporium)

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

House Dust Mite Control Improves Asthma

Per

cen

tage

of

Day

s

Treatment Control

Wheezing Medication use Peak flow drops below 80% of predicted

Murray and Fergusson, 1983

First Line Dust MiteControls

• Pillow cover (<10 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

Bonus!

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

Cat Allergen

• Cat hair

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)

What Works if Pets Stay?

• Keep animals out of patient’s bedroom• Use HEPA or electrostatic air cleaners in

bedroom and living room• Remove carpets and other allergen reservoirs• Use mattress and pillow covers

Bonus!

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

Cockroach Allergy and Asthma Hospitalizations in the Inner City Children

0

0.1

0.2

0.3

0.4

Group 1 Group 2 Group 3 Group 4

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

p=0.001

Common Cockroaches Found in Homes

• American• Oriental• German• Brown-banded

Cockroach Controls

• Integrated pest managementIntegrated 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)

Bonus!

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

Indoor Mold Controls

• 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

Bonus!

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 >24 hrs– Other: CBC, ESR, Stool O&P, TFTs, etc.

Urticaria

“Classic” Cholinergic

Cold - induced Solar Dermatographism

Urticaria -Treatment

• Remove the offending agent• Antihistamines• Avoid ASA or NSAIDs• Steroids• Referral

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

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% foods36% foods, 17% medications, 15%

insect stings– Pumphrey et al, 1996: foodsfoods (peanut and tree nuts) major

cause in north-west England– Novembre et al, 1998: foodsfoods responsible for 50% of

anaphylaxis in children treated in the ER

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 1:1000, 0.01 mL/kg (0.3-0.5 ml)

• I. V. antihistamine (H1, H2 blockers), steroids, fluids, oxygen

• Observation > 4 hours

• Refer for allergy evaluation to identify the trigger

• Clear emergency treatment plan

• Rx self-injectable epinephrine device

Drug Allergy

• IgE-mediated– Hives, anaphylaxis

• Non-IgE-mediated– Maculopapular rash– Serum sickness– Stevens-Johnson

• Anaphylactoid = direct release of histamine– Radiocontrast media– Vancomycin– Opiates

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

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

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 >50% to <2%

*Under 16 years of age: generalized urticaria is not associated with increased risk for ANA upon subsequent stings, not an indication for VIT

Allergy EvaluationAllergy Evaluation

• History and physical exam

• Prick skin testing• Serum allergen-

specific IgE• Challenge

Allergy Diagnosis

• 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

Bonus!

Food Allergen-Specific IgE levels (kU/L) in the Diagnosis of Food Allergy

Egg Milk Peanut Fish Soy Wheat

Reactive if > (no challengenecessary)Possibly reactive (physicianchallenge)Unlikely reactive if < (homechallenge)

7

0.35

15

0.35

14

0.35

20

0.35

65

30

0.35

80

26

0.35

Probabilityof reaction

Sampson HA, JACI, 2001

Bonus!

Atopy Markers and Risk Factors

• Family history, mother>father

• 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

Allergy Prevention• 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

– Cow’s milk / dairy: 6-12 months– Egg: 12-24 months– Peanut, tree nuts, fish, shellfish: >36 months

• Aeroallergen avoidance– Dust mites– Animals

Bonus!

Allergen Immunotherapy• Subcutaneous injections of specific

allergen in gradually increasing doses: environmental allergens, insect venoms

• Generally indicated for subjects who don’t respond well to pharmacotherapy

• Allergen avoidance always recommended

• Useful for AR, asthma, venom allergy; generally not indicated for AD and contraindicated in food allergy

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

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 [Kartagener’s 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

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)

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 1:700 whites; mostly asymptomatic– May be associated with chronic bacterial sinusitis, atopy, autoimmne dz (Crohn’s, 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)

*Treatment: IVIG replacement, antibiotic prophylaxis

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 (ALC<2000/µl)– Reduced CD3+T lymphocytes (<1500/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!!!

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 >15,000 /µl (baseline), eosinophilia,

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

Screening Tests• Antibody:

– Serum IgG, IgA, IgM– IgG to immunizations: tetanus, diphtheria, Strep.

pneumoniae

• T-cell immunity: – Lymphocyte count ( <2000/ul)– T cell enumeration (CD3, CD4, CD8)– HIV serology

• Complement:– CH50

• Phagocytosis:– Neutrophil count– Nitroblue tetrazolium test or other tests for oxidative burst