1. A LLERGY AND I MMUNOLOGY B OARD R EVIEW N OVEMBER 8, 2012

2. T EST Q UESTION True or False. I love daylight savings. A. True B. False

3. INTRODUCTION

4. G ENERAL F ACTS Atopy represents the genetic predisposition to develop allergic diseases Atopic dermatitis Allergic rhinitis Asthma Food allergy A child with one component of atopy syndrome has a 3x greater risk of developing a second component

5. I NFLUENTIAL F ACTORS 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)

6. E NVIRONMENTAL 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

7. Q UESTION #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.

8. E NVIRONMENTAL 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

9. 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)

10. A LLERGIC RHINITIS

11. R HINITIS 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

12. A LLERGIC 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

13. Q UESTION #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.

14. A LLERGIC 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)

15. Q UESTION #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 decongestant B. Intranasal corticosteroid C. Ocular antihistamine D. Oral decongestant E. Oral leukotriene antagonist

16. 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

17. A STHMA … GET EXCITED !! O NLY 29 C ONTENT S PECS

18. P ATHOPHYSIOLOGY Disease of airway inflammation mediated by a variety of cell types, resulting in hyper-responsive airways Airway bronchoconstrictionAirway edemaExaggerated mucus productionAirway hyperresponsivenessAirway remodeling

19. Q UESTION #4 What is the primary mediator during the early phase of an asthma exacerbation? A. Cytokines and chemokines B. Eosinophils C. IgE D. IgA E. T-lymphocytes

20. P ATHOPHYSIOLOGY 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!!!

21. P REDISPOSING 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

22. Q UESTION #5 16-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.

23. T RIGGERS  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 Medications Aspirin NSAIDS Beta Blockers

24. E ARLY 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.

25. C LINICAL 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

26. A STHMA C LASSIFICATION 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

27. Q UESTION #6 You 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. Intermittent B. Mild Persistent C. Moderate Persistent D. Severe Persistent

28.  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

29.  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!

31. Q UESTION #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 agonist C. Nasonex D. Leukotriene receptor antagonist (Montelukast) E. Theophylline

32. O UTPATIENT T REATMENT  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

33. O UTPATIENT T REATMENT  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

35. A LTERNATIVE M EDICATIONS  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

36. A LTERNATIVE M EDICATIONS  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

37. Q UESTION #8 You 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. Rocephin B. Azithromycin C. Both Rocephin and Azithromycin D. Augmentin E. None of the above

38. E XACERBATIONS  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

39. E XACERBATION T REATMENT  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

40. E XACERBATION T REATMENT  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

41. R ISKS OF S EVERITY 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 FEV 1 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

42. S ELF A SSESSMENT 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!

44. U RTICARIA, A NGIOEDEMA, & A NAPHYLAXIS

45. A NAPHYLAXIS 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

46. A NAPHYLAXIS

47. A NAPHYLAXIS - 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

48. A NAPHYLAXIS - TRIGGERS Vaccines Egg: influenza, yellow fever Gelatin, Neomycin: MMR Perioperative Muscle relaxants, latex, antibiotics, opioids, blood products Exercise Can be food-dependent Immunotherapy Idiopathic

49. Q UESTION #9 The 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

50. A NAPHYLAXIS - T REATMENT 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

51. U RTICARIA 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**

52. Q UESTION #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 preservative B. Allergy to dust mite C. Autoantibody to the immunoglobulin E receptor D. Autoimmune thyroid disease E. Systemic mastocytosis

53. C HRONIC U RTICARIA - T RIGGERS 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

54. C HRONIC U RTICARIA - T REATMENT 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

55. A NGIOEDEMA 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

56. F OOD A LLERGY

57. 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

58. F OOD A LLERGY : C LINICAL M ANIFESTATIONS 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

59. O RAL A LLERGY S YNDROME 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

60. O RAL A LLERGY VS A NAPHYLAXIS **

61. F OOD A LLERGY : D IAGNOSIS 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

62. Q UESTION #11 A 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 diet B. Eliminate fruit and acidic juices from the diet C. Perform aeroallergen allergy testing D. Perform food allergy testing E. Refer for a skin biopsy

63. F OOD A LLERGY AND E CZEMA 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

64. I MMUNODEFICIENCIES (G ET R EADY FOR SOME WORDY SLIDES )

65. I MMUNODEFICIENCIES 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

66. I MMUNE 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!

67. Q UESTION #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 immunodeficiency B. Severe combined immunodeficiency C. X-linked agammaglobulinemia D. Wiskott-Aldrich syndrome E. Hyper IgE syndrome

68. A NTIBODY D EFICIENCY S YNDROMES 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)

69. S ELECTIVE I G A D EFICIENCY 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!

70. X- LINKED A GAMMAGLOBULINEMIA (B RUTON ’ 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

71. C OMMON V ARIABLE I MMUNODEFICIENCY 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

72. T RANSIENT H YPOGAMMAGLOBULINEMIA OF I NFANCY 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

74. H YPER I G M ( 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

75. Q UESTION #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 media B. Preterm delivery C. Neisseria meningitis D. Failure to thrive E. Delayed umbilical cord separation

76. C ELLULAR /C OMBINED I MMUNODEFICIENCIES 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*

77. D I G EORGE (22 Q 11 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

78. 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

79. W ISCOTT -A LDRICH 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)

80. A TAXIA -T ELANGIECTASIA 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

81. H YPER -I GE 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

82. Q UESTION #14 An 11 month old boy is being hospitalized for a prolonged febrile illness. His WBC is 32x10 3, 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. HIV B. DiGeorge Syndrome C. Transient hypogammaglobulinema of infancy D. Hyper IgM E. Chronic granulomatous disease

83. P HAGOCYTIC D ISORDERS 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

84. 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 H 2 0 2 production/NADPH oxidase system B and T cell immunity is normal Diagnosis: NBT, DHR assays Treatment? Antibiotics, interferon-gamma, BMT

85. L EUKOCYTE A DHESION D EFICIENCY (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

86. C HEDIAK -H IGASHI SYNDROME Abnormal chemotaxis Oculocutaneous albinism Peripheral neuropathy Easy bruisability Diagnosis: bone marrow smear Lysosomal granules in WBCs Treatment? BMT, frequent antibiotics

87. C OMPLEMENT D ISORDERS 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

88. C OMPLEMENT D EFICIENCY 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

89. S CREENING T ESTS FOR P RIMARY 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

90. Q UESTION #15 You 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) test B. HIV serology C. Immunoglobulin G concentration D. FISH for 22q11 deletion E. T-cell subset assessment

92. S ECONDARY I MMUNODEFICIENCIES Malignancy HIV Asplenia Nephrotic Syndrome

93. E XTRA C ONTENT S PECS

94. R ADIO C ONTRAST M EDIA (RCM) R EACTION 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

95. S KIN T ESTING 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 1 st and 2 nd generation Antidepressants with antihistaminic effect Amitryptiline

96. I MMUNOTHERAPY 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

97. T HE E ND ! YAY