ALLERGY AND IMMUNOLOGY BOARD REVIEW

NOVEMBER 8, 2012

TEST QUESTION

True or False. I love daylight savings. A. TrueB. False

INTRODUCTION

GENERAL FACTS

Atopy represents the genetic predisposition to develop allergic diseasesAtopic dermatitisAllergic rhinitisAsthmaFood allergy

A child with one component of atopy syndrome has a 3x greater risk of developing a second component

INFLUENTIAL FACTORS History of atopy in a first-degree relative

or parent is the greatest risk factor for atopy Neither parent: 10-15% risk One parent: 20-40% risk Both parents: 30-60% risk

Early childcare exposure reduces the risk for development of asthma…“hygiene hypothesis”

Non-genetic risk factors Aeroallergen sensitivity Environmental exposures Diet (mom’s and baby’s)

ENVIRONMENTAL EXPOSURE

Early exposure to tobacco smoke, especially the mother’s, increases the frequency of asthma in children!!!This is even true for babies whose mom smokes

during pregnancy

Passive exposure to cigarette smoke may exacerbate asthma and allergic rhinitis!

1-800-QUIT-NOW

QUESTION #1

You are seeing an 8yo female with atopy syndrome back in clinic after referring her to Allergy/Immunology for some help. Skin prick testing was positive for various indoor allergens, including dog and cat. The family has a dog that has been around since your patient was 3yo. How should you counsel this family regarding their pet?

A. Nothing. The dog is not affecting her symptoms.B. Tell the parents that they must sell the dog or find

someone take her.C. Tell the parents that they must sell the child or find

someone to take her.D. Keep the dog from the bedroom and decrease her

exposure to pillows, carpeted areas, and stuffed animals.E. Bathe the dog once a week and things should be fine.

ENVIRONMENTAL EXPOSURE Identification of indoor allergens is important

Dust mites among most common Animal dander from indoor pets…cat, dog, rodents Cockroach, especially in inner-city areas Mold

Avoidance Pet removal

May not always be correct answer because of attachment Removal/isolation from patient’s bedroom more

likely!! Impermeable covers, HEPA filters, vacuuming

frequently Removal of carpet and stuffed animals No single intervention alone is likely to have a

significant overall effect

DIET Maternal diet during pregnancy and/or

breastfeeding has NOT been shown to significantly alter the incidence of atopy Restricting the mother’s diet will not be the correct

answer!!!

Breastfeeding for the first 3-6 months after birth reduces the risk of atopic dermatitis in “at risk” babies The AAP recommends exclusive breastfeeding for at

least 4 months with supplementation of hypoallergenic formula if needed in “high risk” newborns (both parents or one parent and one sibling have atopy)

ALLERGIC RHINITIS

RHINITIS

Rhinitis: Inflammation of the membrane lining the nose and/or postnasal drainage

Chronic rhinitis can be either allergic or non-allergic Stimuli (allergens, medications, hormones) cause

mast cells and basophils to degranulate Chemical mediators are released causing rhinorrhea

and nasal congestion Histamine release causes sneezing and itching

Allergic rhinitis: IgE-mediated hypersensitivity reaction to specific allergens

ALLERGIC RHINITIS History

Nasal congestion: mouth breathing, snoring, nasal voice Nasal irritation: sneezing, nasal pruritis, nose blowing,

sniffing, snorting, coughing Itchy eyes and postnasal drip Impact on quality of life, seasonality, triggers, alleviating

factors, and medication use are also important Comorbidities…sinusitis and otitis media

Physical exam Pale, edematous turbinates Cobblestoning of posterior OP from lymphoid hyperplasia “Allergic shiners” from venous engorgement Dennie lines from edema Allergic salute: transverse nasal crease

QUESTION #2

What is the MOST common cause of perennial (persistent) allergic rhinitis?

A. Using Afrin (a nasal decongestant) for longer than a week.

B. Cold weather or change in temperatures.C. Eggs, wheat, milk, peanuts, and soy.D. Outdoor allergens…different pollens and grasses.E. Indoor allergens like animal dander, molds, and

dust mites.

ALLERGIC RHINITIS Triggers

Seasonal rhinitis: outdoor plant allergens or specific molds that vary depending on the time of year

Perennial rhinitis: indoor allergens such as dust mites and animal dander

Testing to identify allergen hypersensitivity Percutaneous (prick or puncture) skin testing remains the

most specific and cost-effective diagnostic modality RAST testing (for IgE) in blood can also be used

Nasal eosinophilia (nasal smear >4% eosinophils)

QUESTION #3

A 12yo girl presents with recurrent rhinorrhea, sneezing, ocular pruritis, and nasal congestion each spring and fall. On PE, she has bilateral conjunctival erythema, enlarged and pale nasal turbinates, and a transverse nasal crease.

Which medication will be your BEST first choice medication for symptom improvement?

A. Intranasal decongestantB. Intranasal corticosteroidC. Ocular antihistamineD. Oral decongestantE. Oral leukotriene antagonist

TREATMENT Allergen avoidance = initial management

Intermittent symptoms: indoors during high pollen times, AC during spring and fall pollen seasons

Indoor allergens: decrease humidity (<50%), bed/pillow covers; remove pets from home OR decrease exposure by eliminating from bedroom and areas with rugs/pillows/heavy upholstery

Intranasal corticosteroids: first-line pharmacotherapy Regular use can reduce nasal blockage, rhinorrhea,

sneezing, and nasal itching Most common adverse effect = epistaxis

Antihistamines (H1 or H2) Decreased sneezing, itching, and rhinorrhea NOT effective at treating congestion

ASTHMA…GET EXCITED!!ONLY 29 CONTENT SPECS

PATHOPHYSIOLOGY Disease of airway inflammation mediated by a

variety of cell types, resulting in hyper-responsive airways

Airway edema

Airway remodeling

QUESTION #4

What is the primary mediator during the early phase of an asthma exacerbation?

A. Cytokines and chemokinesB. EosinophilsC. IgED. IgAE. T-lymphocytes

PATHOPHYSIOLOGY Early phase

IgE mediated Mast cells and basophils

degranulate causing bronchospasm

Short-acting beta agonists!!

Late phase Inflammatory Increased bronchial

hyperresponsiveness 4-12 hours after exposure

to environmental insult STEROIDS!!!

PREDISPOSING CONDITIONS

Family history of asthma Atopy syndrome: allergic rhinitis and eczema

Most children with asthma (60-80%) are sensitized to at least 1 aeroallergen Common indoor allergens: house dust mite, mold,

cockroach, and animal dander Skin testing should be considered for any child with

persistent asthma

Exposure to tobacco smoke Potent airway irritant More likely to have mod-severe asthma with

decreased lung function

QUESTION #516-year-old boy who runs on his high school cross-country

team has been having trouble with coughing and wheezing during exercise. He has a history of intermittent asthma that is well controlled when he is not running. His coach is worried that he may have exercise-induced asthma (EIA). Which of the following is NOT characteristic of this diagnosis??

A. EIA is sometimes the only presentation of asthma.B. The symptoms often resolve with or without medication

once the exercise is stopped.C. Long acting beta agonists are the preferred treatment

and the effect will continue even with long-term use.D. The onset of wheezing 5 minutes after exercise starts

with resolution within 20-30 minutes after stopping.E. Is often a sign of poorly controlled/more severe asthma.

TRIGGERS

Exercise induced asthma: Coughing and wheezing after 5-6 minutes of exercise, gradual improvement after 20-30 minutes of rest (with or without med); smog increases severity!!

Can be the only presentation OR a sign of underlying, poorly controlled/more severe asthma

MedicationsAspirinNSAIDS

Beta Blockers

EARLY WHEEZING

Transient wheezers cease to wheeze after age 3 Often associated with a LRTI, especially RSV

RSV and future development of asthma… Exact data varies Risk increases with severe infection (ie. hospitalization)

More than 80% of infants with a history of wheezing in the first postnatal year (especially with URIs) do not wheeze after age 3

Atopic wheezers are most likely to develop persistent asthma Kids with early onset asthma (<3y) with a parental

history of asthma, confirmed atopic dermatitis, or sensitization to aeroallergens are least likely to outgrow asthma.

CLINICAL MANIFESTATIONS

Cough (may be the only symptom) Nighttime symptoms are common!

Wheezing Difficulty breathing “Chest tightness” Symptoms often worsen in presence of triggers

Be sure discharge planning includes a full assessment of potential triggers in the home, school, or neighborhood!

Other signs of atopy

ASTHMA CLASSIFICATION Severity is initially best determined at time of

diagnosis, before starting therapy Determined by the most severe level of symptoms Exercise-induced symptoms do not count towards severity

Four categories: intermittent, mild/moderate/severe persistent

The most important distinction is between intermittent and persistent asthma because all individuals with persistent asthma should be started on long-term controller medication (inhaled corticosteroids)

2007 Guidelines breaks down into 3 age categories

QUESTION #6You are rounding on Purple team with Dr. Hescock.

You are presenting a 7yo male patient to the team who is here with status asthmaticus. Dr. Hescock asks you to classify his asthma at baseline. Per mom, he usually coughs one night per week and uses his albuterol at home 4-5 days/week. He saw a pulmonologist last month for PFTs, and his FEV1 was 75%. How would you BEST classify his asthma?

A. IntermittentB. Mild PersistentC. Moderate PersistentD. Severe Persistent

Major risk factors (one required): parental history of asthma, eczema, aeroallergen sensitivity

Minor risk factors (2 required): sensitization to foods, more the 4% eosinophilia, wheezing apart from colds

PFTs should be performed at the initial time of asthma diagnosis (if old enough…5-6 years)

PFTs should also be assessed every 6-12 month in ALL patients with persistent asthma!

QUESTION #7

You have determined that a 4yo patient you are seeing in clinic today has mild persistent asthma. You have given mom a prescription for her albuterol MDI. What is the other MOST important prescription you need to write?

A. Inhaled corticosteroid B. Long acting beta agonistC. NasonexD. Leukotriene receptor antagonist (Montelukast)E. Theophylline

OUTPATIENT TREATMENT Short-acting beta agonists (rescue med)…work on the

early (bronchospasm) phase

Treatment of ANY persistent asthma should include a long-term controller medication for prevention.

First-line = inhaled corticosteroids Decreases bronchial inflammation and hyper-

responsiveness Block the late response to allergen (inflammatory

phase) Most effective anti-inflammatory medication for asthma

Reduce asthma symptoms Improve lung function Reduce acute exacerbations Reduce the risk of death from asthma

OUTPATIENT TREATMENT Inhaled Corticosteroids

Side effects: oral candidiasis, dysphonia (hoarseness), reflex cough, bronchospasm Can be reduced by using a “spacer” with MDI, slowing the rate

of inhalation, as well as rinsing the mouth with water after use

High dose ICS may have an initial early affect on growth velocity, but no data suggests effect on final adult height; no known decrease in bone mineral density

ALTERNATIVE MEDICATIONS

Leukotriene receptor antagonists (montelukast and zafirlukast) Interfere with the action of leukotrienes…potent

inflammatory mediators that are released from mast cells, eosinophils, and basophils

Alternative (not preferred) therapy for patients with mild persistent asthma

“Add-on” therapy for patients who do not achieve good control with medium-dose ICS

Theophylline Omalizumab Cromolyn sodium and nedocromil

ALTERNATIVE MEDICATIONS

Long acting beta agonists (LABA) 12 hours of bronchodilation by stimulation beta-2

receptors in the airway Increased cAMP Relaxation of smooth muscle

Available as dry powder inhaler (formoterol) or in combination with ICS (salmeterol/formoterol)

NOT To be used to treat acute exacerbations Anti-inflammatory…so do NOT use as monotherapy Prevent exercise-induced bronchospasm, but effect

deteriorates with long-term administration Preferred “add-on” medication in kids > 12 years

QUESTION #8You are in the ER seeing a patient with asthma for

increased WOB that started with the weather change yesterday. His last admission was during the winter last year. He is afebrile and other than his wheezing and increased WOB with a dry cough, ROS is negative. On PE, you hear diffusely decreased breath sounds, wheezes, and no crackles. His CXR is shown. What other medication would you start besides Albuterol and Steroids?

A. RocephinB. AzithromycinC. Both Rocephin and AzithromycinD. AugmentinE. None of the above

EXACERBATIONS Patients who have any degree of asthma severity can

have a severe exacerbation.

Symptoms of severe obstruction Dyspnea at rest, inability to speak whole phrases Cyanosis, accessory muscle use (retractions) Quiet breath sounds (NO wheeze = bad) Peak flow less than 40% predicted or personal best Failure to respond to initial treatments

Patients with exacerbations uncontrolled by home medications should present to the ER!

Atelectasis on CXR is common Antibiotics are NOT indicated unless there is true

evidence of bacterial infection CPT is not helpful

EXACERBATION TREATMENT An inhaled short-acting beta agonist is first-line

(albuterol, levalbuterol) Relax smooth muscle within minutes, peak effect at15-30

minutes, wears off at 4-6 hours Often patients will need a continuous treatment Side effects: tachycardia, tremulousness, irritability,

hypokalemia Oxygen if increased WOB or with low O2 Saturations Consider MIVFs

Patients are prone to increased HR because of chest hyper-expansion that impedes venous return

Albuterol increases HR even further Ipratropium bromide (anticholinergic) in ER can

decrease admission rates

EXACERBATION TREATMENT

For severe exacerbations that are unresponsive to SABAs alone…systemic corticosteroids to treat late phase Improve airway responsiveness to SABAs, improve lung

function (FEV1) and oxygenation, and decrease the risk of relapse from acute exacerbation

2mg/kg/day (3-10 days depending on severity) NO difference between IV/PO steroids in terms of efficacy IF a patient is having a moderate to severe exacerbation

with increased WOB, IV steroids should be ordered Can give higher doses…varies but 1mg/kg q6h and possibly

up to 2mg/kg q6h!

Magnesium sulfate IV and MORE…but no content specs on this

RISKS OF SEVERITY

Risk factors for ICU admission OR higher rate of death One or more life-threatening exacerbations of asthma Severe asthma requiring chronic oral steroids Abnormal FEV1 Poor adherence Poor control of daily asthma symptoms Frequent daily short-acting beta agonist use

Excessive use (>2 days/week) has been associated with poorly controlled asthma and an increased risk of hospitalization and death!

Low socioeconomic status, family dysfunction Patient psychological problems…depression/stress

SELF ASSESSMENT

Teaching the patient and/or family ways to recognize exacerbations is extremely important to patient outcome!

Counseling the family at EVERY visit regarding proper use of daily controller medications and rescue medications is essential to good control!

Be sure your patients know when an ER visit is necessary!

URTICARIA, ANGIOEDEMA, & ANAPHYLAXIS

ANAPHYLAXIS

Immediate and potentially life-threatening reaction to an allergen

Symptoms typically develop within minutes up to 2 hours Rare cases of delayed reactions >2hrs after

exposure Most common symptoms = cutaneous

Pruritus, flushing, urticaria, angioedema Occur in up to 90% of patients

ANAPHYLAXIS

ANAPHYLAXIS - TRIGGERS

Foods Most common: milk, egg, soy, wheat,

peanut/tree nut, seafood Drugs

Most common: Penicillin Low-risk of cephalosporin cross-reactivity

Other antibiotics (sulfa, etc), aspirin, NSAIDs, chemo

Insects Hymenoptera (vespids, bees, stinging ants) Large local reactions increase risk for

anaphylaxis Latex

Rubber tree antigens

ANAPHYLAXIS - TRIGGERS

Vaccines Egg: influenza, yellow fever Gelatin, Neomycin: MMR

Perioperative Muscle relaxants, latex, antibiotics, opioids,

blood products Exercise

Can be food-dependent Immunotherapy Idiopathic

QUESTION #9The parents of a 10-year-old boy who has a peanut allergy ask

your advice on treatment of food allergy reactions at school. Last year, their son started itching diffusely and had difficulty breathing during lunchtime after accidentally eating some of his friend's chocolate candy bar that contained peanuts. The child is allowed to carry his own self-injectable epinephrine at school. His current weight is 90 lb (41 kg).

Of the following, the BEST advice for the child, if a similar situation occurs, is to

A. Have the school call emergency services (911), who should evaluate and administer epinephrine if needed

B. Have the school nurse observe the child for 10 to 15 minutes while calling his parents

C. Immediately administer 0.15 mg of self-injectable epinephrine

D. Immediately administer 0.30 mg of self-injectable epinephrine

E. Take an oral antihistamine immediately

ANAPHYLAXIS - TREATMENT

Most important = recognize symptoms!! Early administration of epinephrine

Best route = IM (lateral thigh) Dose = 0.01mg/kg (max. 0.5mg) EpiPen

0.15mg for <30kg 0.30mg for >30kg

Corticosteroids to help prevent the late-phase or biphasic reaction 20% will have symptoms 4-24hrs after initial

reaction +/- H1-antihistamines

URTICARIA

Can be associated with anaphylaxis; but often occurs without systemic symptoms

Typical lesion: raised, erythematous, pruritic or burning, resolves within 24 hours

Acute vs chronic Acute: symptoms last <6 weeks

60% are due to proven or probable infection (usually viral)**

Chronic: symptoms lasting > 6 weeks Do NOT order skin or serum IgE food testing without

substantial clinical history**

QUESTION #10

A 10yo M presents for evaluation of hives that have occurred daily over the past 4 months. They are raised, erythematous, pruritic, 1-2cm lesions on his trunk and extremeties. They resolve spontaneously in a few hours and can occur at any time of day or night. His parents are frustrated by the lack of response to changes in soap and laundry detergents. What is the MOST likely cause of this child’s hives?

A. Allergy to food additive or preservativeB. Allergy to dust miteC. Autoantibody to the immunoglobulin E receptorD. Autoimmune thyroid diseaseE. Systemic mastocytosis

CHRONIC URTICARIA - TRIGGERS Autoimmune: 30-50%

Circulating autoantibody directed against IgE receptor on mast cells and basophils

Autologus serum skin test (ASST) positive Artificial flavors, colors, additives: 1-2% Physical urticaria:

Dermatographism Heat-induced Cold-induced Pressure-induced Contact

Localized IgE reaction to food, enviornmental, animal, etc Solar

Unknown

CHRONIC URTICARIA - TREATMENT

Goal = block histamine and tryptase Most common medication: antihistamines

Second-generation H1-antihistamines: first line therapy Cetirizine, loratidine, fexofenadine, etc Low adverse effects Can increase dose up to 4x’s usual dose

First-generation H1-antihistamine for rescue Diphenhydramine, hydroxyzine

Other medications (no approved indication, but clinical use suggests they are helpful) H2-antihistamines, leukotriene receptor

antagonists, thyroxine, plasmaphoresis, IVIG, cyclosporine, colchicine, dapsone, sulfasalazine, omalizumab, corticosteroids

ANGIOEDEMA

Transient swelling of the dermis or subcutaneous tissue

Can be a symptom of anaphylaxis; can occur during episodes of urticaria

Causes: Hereditary: 3 types

Type 1 = most common; low C1 esterase inhibitor (C1INH) concentration Inability to stop the complement cascade low C4

Acquired Associated with lymphoproliferative disorders,

autoantibodies to C1INH Idiopathic (most common) Secondary to ACE inhibitors

FOOD ALLERGY

FOOD ALLERGY Immune-mediated adverse reaction to foods Symptoms involve skin, GI tract, respiratory Can be IgE and non-IgE mediated

Common foods causing allergy: Milk, eggs, soy, peanut/tree nut, wheat, seafood

Milk, egg, and soy allergies typically outgrown by age 5

Peanut, tree nut, and seafood allergies are rarely outgrown

90% of food-allergic individuals demonstrate clinical response to only 1 or 2 foods

FOOD ALLERGY: CLINICAL MANIFESTATIONS

IgE: starts within minutes up to 2 hours Ranges from cuteanous reaction to anaphylaxis

Non IgE-mediated: Food-induced proctocolitis, pulmonary

hemosiderosis, celiac disease Mixed IgE and non-IgE

Atopic dermatitis, esosinophilic esophagitis

ORAL ALLERGY SYNDROME

IgE-mediated allergic manifestation affecting the oropharynx Tingling/itching of lips, palate, tongue Occasionally abdominal discomfort, nausea/vomiting No symptoms when the food is cooked or processed

Affects 50% of adults with allergic rhinitis to inhalent pollens Most common adult food allergy Due to cross-reactivity between proteins of pollens

and those in fruits/vegetables Birch: apple, plum, peach, nectarine, cherry, almond Ragweed: melon, banana, tomatoe Grass: melon, kiwi Mugwort: celery, spices, carrot

ORAL ALLERGY VS ANAPHYLAXIS**

FOOD ALLERGY: DIAGNOSIS

History: Most important! Skin Prick Testing Radioallergosorbent Test (RAST)

Identify food-specific IgE antibodies Typically correlates closely with skin test** Indicated when oral antihistamines cannot be

stopped, when pt has dermatographism, or if h/o anaphylaxis to the agent being tested

Oral Food Challenge Double-blind, placebo-controlled Food

challenge Gold standard

QUESTION #11A 12-month-old boy presents with a 7-month history of

a worsening skin rash. The rash is pruritic and involves his neck, anterior and posterior trunk, antecubital and popliteal fossae, and hands and feet. Use of a moisturizer and topical corticosteroid has resulted in some improvement. The remainder of his past medical history is unremarkable. Physical examination is consistent with severe atopic dermatitis. Of the following, the MOST helpful next step is to:

A. Eliminate milk, eggs, soy, and wheat from the dietB. Eliminate fruit and acidic juices from the dietC. Perform aeroallergen allergy testingD. Perform food allergy testing E. Refer for a skin biopsy

FOOD ALLERGY AND ECZEMA

30-40% of children with moderate-severe eczema have IgE-mediated food allergy

In some infants, food ingestion may result in immediate worsening of eczema severity However, most infants do not demonstrate this

immediate reaction Food avoidance should be guided by the

dietary history, eczema severity, and results of allergy testing

Aeroallergens (mold, trees, weeds) are not associated with eczema in infants

IMMUNODEFICIENCIES (GET READY FOR SOME WORDY SLIDES)

IMMUNODEFICIENCIES

Group of disorders that increase susceptibility to infection, malignancy, and autoimmunity

Can be congenital or acquired

Common clinical findings in many types: Recurrent or chronic respiratory infections 2+ episodes of bacterial PNA 5+ episodes of otitis media in 1 year or 7 in 2

years Recurrent or persistent sinusitis

IMMUNE SYSTEM

Antibody-mediated (B-cells) Immunodeficiency due to subnormal

immunoglobulin levels OR defective specific antibody responses

Cell-mediated (T-cells) Typically cause a combined immunodeficiency

because T-cells provide signals for B-cell differentiation

Phagocytosis Complement system

Defects of any component can cause an immunodeficiency!

QUESTION #12 A 17-year old boy presents with a 3-4 year

history of receiving antibiotics every other month for sinusitis and pneumonia. He has also had one episode of diarrhea due to Giardia. CT of the lungs shows bronchiectasis. He has low IgG, IgA and IgM concentrations but normal numbers of T and B cells. What is the most likely diagnosis?

A. Common variable immunodeficiencyB. Severe combined immunodeficiencyC. X-linked agammaglobulinemiaD. Wiskott-Aldrich syndromeE. Hyper IgE syndrome

ANTIBODY DEFICIENCY SYNDROMES

Presentation Presents after 4-6mos of age

Often into adulthood Recurrent bacterial

sinopulmonary infections Unexplained bronchiectasis Diarrhea secondary to

Giardia or enterovirus Pathogens: gram-positive

pyogenic bacteria; extracellular encapsulated organisms (S. pneumoniae, H influenza type B, GAS); enterovirus

Typically do not have growth problems

Types to know: Selective IgA deficiency

X-linked agammaglobulinemia

Common Variable Immunodeficiency

Transient hypogammaglobulinemia of infancy

Hyper-IgM (combined B and T cell problem)

SELECTIVE IGA DEFICIENCY

Low or absent IgA Other Ig levels are normal Cell-mediated immunity is intact Can be asymptomatic Sinusitis, otitis, diarrhea (giardia)

Treatment? symptomatic Anaphylaxis with IVIG!

X-LINKED AGAMMAGLOBULINEMIA (BRUTON’S)

Infections begin at 6-9 months Pneumonia, otitis, sinusitis are prevalent Infections with pneumococcus,

streptococcus, and Haemophilus Recurrent enteroviral infections Low/absent immunoglobulins, NO mature B-

cells Normal or increased T-cell number

Absent/decreased tonsils and lymph nodes

Treatment? IVIG, avoid live vaccines

COMMON VARIABLE IMMUNODEFICIENCY Onset 15-35 years of age Varying degrees of immunoglobulin deficiency and

impaired antibody responses Low IgG, IgA, IgM (Typically 2 subtypes will be low; may be all) Poor response to protein (DTaP) and polysaccharide (PCV)

vaccines Pneumonia, bronchiectasis, sinusitis, GI infxns Normal number of mature B cells

But fail to differentiate Intact cell-mediated immunity, but depressed T-cell

function over time Increased incidence of malignancy (NHL, gastric

carcinoma), autoimmunity (RA, thyroid abnormalities)

Treatment? IVIG

TRANSIENT HYPOGAMMAGLOBULINEMIA OF INFANCY

Self-limited antibody deficiency No intrinsic B cell deficiency; decreased T-helper

functions Normal infants have time of low Ig levels at

3-6 months In some infants this persists

Detected at 1-2 years of age Typically resolved by 3-6 years of age

Low IgG, low/normal IgA, normal IgM B cells present, normal number

Treatment? supportive

HYPER IGM (COMBINED B AND T CELL PROBLEM)

X-linked Severe respiratory infections, sinusitis IgM is high, IgG, IgA, IgE are very low

Absence of CD40 ligand found on T cells No Ig class switching

Normal T-cell number/cellular function, but T-cell immunity weakens with time Can be classified as combined deficiency

Associated with autoimmunity, malignancy

Treatment? IVIG

QUESTION #13

You are seeing a 3-month old baby with suspected severe combined immunodeficiency (SCID). Of the following options, which would be the MOST suggestive for SCID?

A. Acute otitis mediaB. Preterm deliveryC. Neisseria meningitisD. Failure to thriveE. Delayed umbilical cord separation

CELLULAR/COMBINED IMMUNODEFICIENCIES

Presentation: Present in first few months

after birth FTT, chronic diarrhea,

overwhelming infections Pathogens: gram-negative

bacteria, fungi, protozoa, viruses, mycobacteria, PCP pneumonia

Respond poorly to antibiotics

GVHD High incidence of

malignancy Poor survival beyond infancy

Types to know: DiGeorge

Severe Combined immunodeficiency

Wiscott-Aldrich

Ataxia Telangiectasia

Hyper-IgE*

DIGEORGE (22Q11 DELETION)

Defect in embryogenesis: heart, thymus, parathyroid

Hypoparathyroidism Hypocalcemia Abnormal facies, cleft palate Absent thymus Decreased number of T cells Normal number of B cells

May have low Ig levels or poor specific antibody responses

Treatment? Thymus transplant, BMT

SCID

Life threatening infections shortly after birth FTT, oral thrush, chronic diarrhea, pneumonia

(especially PCP), sepsis, dermatitis Susceptible to overwhelming viral infection

Varicella, CMV, herpes Blood transfusions cause GVHD Failure of lymphoid precursors to differentiate

into B cells and T cells Both T-cell and B cell immunity markedly

decreased

Treatment? BMT

WISCOTT-ALDRICH

X-linked, WASP gene Triad: eczema,

thrombocytopenia, recurrent sinopulmonary infections

Small platelets Poor antibody response to

polysaccharide antigens and defective T-cell function

Normal B and T cell number

Associated with autoimmune disorders, malignancy (hematologic)

ATAXIA-TELANGIECTASIA

AR Occulocutaneous telangiectasia Cerebellar ataxia

Presents first (around 2yo) Recurrent sinopulmonary infections;

bronchiectasis Lymphopenia, normal or depressed T-cell

numbers No response to delayed hypersensitivity tests Variable low Ig levels (IgA, IgG2, IgG4) Increased susceptibility to malignancy

Increased sensitivity to radiation, defective DNA repair, frequent chromosomal breakages

HYPER-IGE

Autosomal Dominant Eczema and recurrent bacterial infections

of skin, lungs, middle ear, sinuses Boils, abscesses, pneumatoceles Most common: S. aureus, Candida infections Very high IgE Eosinophilia +/- problems with chemotaxis Associated with scoliosis, retained primary

teeth, coarse facies

Treatment? Antibiotics, steroids

QUESTION #14An 11 month old boy is being hospitalized for a

prolonged febrile illness. His WBC is 32x103, with 82% neutrophils, 6% bands, and 12% lymphocytes. He has a large left upper lobe infiltrate and bronchoscopy was positive for Aspergillus. He has multiple enlarged mediastinal lymph nodes and surgical biopsy reveals necrotizing granulomas. What is the most likely diagnosis?

A. HIVB. DiGeorge SyndromeC. Transient hypogammaglobulinema of infancyD. Hyper IgME. Chronic granulomatous disease

PHAGOCYTIC DISORDERS

Presentation: Recurrent dermatologic

bacterial infections Pathogen: catalase-

positive bacteria (S. aureus, E. Coli, Serratia)

Subcutaneous, lymph node, lung, liver abscesses

Pulmonary infections including abscess and pneumoatocele formation

Bone and joint infections Peridontal disease Delayed separation of cord

Types to know: Chronic

granulomatous disease

Leukocyte adhesion deficiency

Chediak-Higashi syndrome

CGD

XL or AR Disorder of bactericidal function of neutrophils Granulomatous lesions of skin, lymph node, lung Liver, spleen, lung abscesses Infections with catalase-positive bacteria (staph,

El coli, Klebsiella, Proteus) and fungal (Aspergillus, candida)

Also see Serratia, nocardia, Burkholderia infxns Defective H202 production/NADPH oxidase system B and T cell immunity is normal Diagnosis: NBT, DHR assays Treatment? Antibiotics, interferon-gamma, BMT

LEUKOCYTE ADHESION DEFICIENCY (LAD)

AR Defect in chemotaxis VERY high WBC Delayed umbilical stump separation;

omphalitis Gingivostomatitis/peridontal disease,

skin infections Delayed wound healing Infected areas have no pus/minimal

inflammation

Treatment? BMT

CHEDIAK-HIGASHI SYNDROME

Abnormal chemotaxis Oculocutaneous

albinism Peripheral neuropathy Easy bruisability Diagnosis: bone

marrow smear Lysosomal granules

in WBCs Treatment? BMT,

frequent antibiotics

COMPLEMENT DISORDERS

Presentation: Recurrent bacterial

infections with extracellular encapsulated organisms (S. pneumo, H. influenza)

Recurrent meningococcal or disseminated gonorrheal infection

Increased incidence of autoimmune disease

Severe or recurrent skin and respiratory tract infections

Angioedema of face, hands, feet, GI tract

Types to know: C5-9 terminal

complement deficiency

C1 esterase inhibitor deficiency

C2, C3, C4 deficiency

COMPLEMENT DEFICIENCY

C2 most frequently deficient protein Terminal components (C5-C9) Deficiency

Recurrent Neisseria infections Total complement (CH50) is very low/absent Treatment? Antibiotics, immunizations,

symptomatic care

SCREENING TESTS FOR PRIMARY IMMUNODEFICIENCIES

CBC with differential CXR, sinus xrays, bone films (if warranted by

history) Cultures, if appropriate

Testing for antibody and cellular immune responses Investigate phagocytic and complement

disorders when there are normal antibody and celluar immune responses

QUESTION #15You are seeing a baby in the NICU for

hypocalcemia. You note low-set ears, hypertelorism and a murmur on exam. Lab work shows a low total T cell count, with normal B cell number. Which of the following tests is most likely to be diagnostic?

A. Nitro Blue Tetrazolium (NBT) testB. HIV serologyC. Immunoglobulin G concentrationD. FISH for 22q11 deletionE. T-cell subset assessment

SECONDARY IMMUNODEFICIENCIES

Malignancy HIV Asplenia Nephrotic Syndrome

EXTRA CONTENT SPECS

RADIOCONTRAST MEDIA (RCM) REACTION

NonIgE-mediated Initially, reactions were believed to be due to

the iodine But studies have demonstrated that the

osmolarity of the solution is the primary cause Pre-treating individuals who have a history of

RCM reactions with corticosteroids and a combination of histamine-1 and histamine-2 antihistamines significantly reduce the risk of reaction

SKIN TESTING

Indications for skin testing Severe atopic dermatitis Allergic rhinitis unresponsive to routine

treatment Food allergy Asthma triggered by airborne allergens Vaccine or drug allergy Latex allergy

Antihistamines alter the results of skin testing 1st and 2nd generation Antidepressants with antihistaminic effect

Amitryptiline

IMMUNOTHERAPY

Used to treat allergic rhinitis, allergic asthma, allergic conjunctivitis, stinging insect hyepersensitivity Most effective in treating allergic rhinitis**

There is a risk for anaphylaxis!! Mandatory 30 minute waiting period after

injection of immunotherapy Epinephrine is the treatment

Antihistamines, corticosteroids too

THE END! YAY