pediatric board review allergy & immunology david j. resnick, m.d. associate clinical prof. of...
TRANSCRIPT
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Pediatric Board ReviewAllergy & Immunology
David J. Resnick, M.D. Associate Clinical Prof. of Pediatrics
Columbia UniversityThe New York Presbyterian Hospital
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Goal of Talk
Identify common pediatric allergic diseasesLearn to diagnose and manage these conditionsDiscuss the presentation and diagnoses of
primary immunodeficienciesNinety percent of the audience will be awake at
the end of the talk
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APC
Th1
neutrophils
T cell
Th2mast
B cell
eosinophil
NaïveT cell
Il-4
Il-12
TNF
IFN
T Regulator
IL-3, 9
Il-4, 9 &13
Il-3,5,9,GM-CSF
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Late-phase reactionLate-phase reactionLate-phase reactionLate-phase reaction
PrimingPrimingPrimingPriming
HyperresponsivenessHyperresponsivenessHyperresponsivenessHyperresponsiveness
Early InflammationEarly Inflammation Late InflammationLate Inflammation
Mast cellMast cell
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Mast Cell
HistamineLeukotrienes
PAFProstaglandins
ECFNCF
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Eosinophil
PAFLTC4
Major Basic ProteinCationic Protein
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Immediate and Late Reactions in IgE-mediated Hypersensitivity
Immediate ReactionsImmediate Reactions
Late ReactionsLate Reactions
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Gell and CoombsAllergic Mechanisms
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Classification of Allergic Diseases
• Type I- allergic rhininitis/conjunctivitis, allergic asthma, anaphylaxis, drug reactions, latex allergies, venom allergies, hives, food allergies
• Type II – autoimmune hemolytic anemia• Type III –serum sickness (PCN, Ceclor)• Type IV – contact dermatitis (chemicals in latex
gloves, latex, poison ivy, nickel)• Other – direct mast cell release
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An 18 yr old presents with hives, pruritis, SOB, after eating at a seafood restaurant. There is a history of a shrimp allergy but he ordered tuna .His BP is 120/70, Oxygen sat was 92% on RA.The most appropriate action is to:A) Administer SC Epinephrine in the deltoidB) Administer IM BenadrylC) Administer PO BenadrylD) Administer IM Epinephrine in the deltoidE) Administer IM Epinephrine thigh
11A) A
dminister S
C Epineph...
B) Administ
er IM
Benadryl
C) Administ
er PO Benad
ryl
D) Administ
er IM
Epinep...
E) Administ
er IM
Epinep...
0% 0% 0%0%0%
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Signs & Symptoms of Anaphylaxis• Respiratory- hoarseness, dysphagia, cough, wheezing,
SOB, tightness in throat, rhinorrhea, sneezing• Cardiovascular- faintness, syncope, arrhythmia,
hypotension• Skin- flushing, pruritus, urticaria angioedema, • Gastrointestinal- nausea, abdominal pain, vomiting,
diarrhea• Mouth- edema & pruritus of lips tongue and palate• Other sites- uterine contractions, conjunctival edema,
feeling of impending doom
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Triggers of Anaphylaxis• Foods- children- peanuts, nuts, fish, shellfish
infants-milk eggs, wheat, soy (contamination commonly happens at restaurants)
• Medications - penicillin & derivatives, cephalosporins, tetracycline, sulfonamides, insulin, ibuprofen
• Allergen vaccines• Latex • Insect Venom• IV contrast material (Anaphylactoid Reaction)
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Acute Treatment of Anaphylaxis
IM Epinephrine is the first line therapy for Anaphylaxis. This is almost always the answer to anaphylaxis on Board questions.
• Early recognition and treatment– delays in therapy are associated with fatalities
• Assessing the nature and severity of the reaction• Brief history
– identify allergen if possible• initiate steps to reduce further absorption
• General Therapy– supplemental oxygen, IVF, vital signs, cardiac monitoring
• Goals of therapy– ABC’s
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Tx Anaphylaxis 2
• Oxygen• Benadryl IM 1mg/kg• Steroids• IV fluids• Nebulized albuterol• H2 blockers• Epinephrine/Dopamine/Norepinephrine
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Differential Diagnosis of Anaphylaxis
• Vasovagal- hypotension, pallor, bradycardia diaphoresis, no hives or flushing
• Scombroidosis – hives, headache, nausea, vomiting, Klebsiella & Proteus produce saurine (Spoiled Mackerel, Tuna)
• Carcinoid –flushing, diarrhea, GI pain, • MSG – flushing, burning, chest pain, headache• Angioneuroticedema Hereditary/Acquired• Panic attacks• Systemic mastocytosis- mastocytomas
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A 10 year old presents with an insect sting that occurred yesterday and now has redness and swelling localized to the arm where he was stung. The redness extended to the entire forearm. There is no fever, chills, SOB or any generalized response.This reaction is best characterized by:
A) CellulitisB) Large local reactionC) Normal reactionD) AnaphylaxisE) Toxic reaction
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A 5 year old presents with hives, SOB, dizziness, and drop in BP, after being stung by an insect. Which of the following statements is true :• 1) Epinephrine SC is the treatment of choice• 2) The chance of having another anaphylactic
reaction to a similar sting is 10%• 3) This patient needs immunotherapy• 4) IV Epi should be given• 5) Get an allergy consult to perform testing to
determine what stung him
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Classification of Insect Reactions• Immediate- within 2-4 hours
– Local reactions- swelling and erythema extending from the insect bite (no antibiotic tx)
– Systemic reactions- are generalized and involve signs and symptoms at a site remote from the sting
• Delayed reactions- can occur days later– Swelling and erythema– Serum sickness –fever, hives, lymphadenopathy– Guillain-Barre syndrome– Glomerulonephritis– Myocarditis– Fever, myalgia, and shaking chills between 8-24 hrs. post
sting
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Toxic reactions• Usually results from multiple simultaneous stings• Similar clinical characteristics of anaphylaxis• Differentiation between a toxic reaction and
anaphylaxis may be difficult• Some patients may develop IgE antibodies after a
toxic reactions and may be at risk for developing an allergic reaction to subsequent stings
• Reaction is probably due to vasodilation from chemicals of the sting
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Indications for Venom ITReaction to sting Venom Immunotherapy
Anaphylaxis (More than cutaneous reaction)
Yes
Cutaneous eruptions
Age 15 and younger
Older than 15
No
Yes
Large local reaction Not required but increased chance of anaphylaxis
Normal Reactions No 22
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A 10 yr old presents with a 1 yr hx of abdominal pain, bloating, diarrhea I hr after eating dairy. PE normal and negative guaiac. The most likely cause of his symptoms is
1) Oral allergy syndrome2) Milk protein allergy3) Allergic eosinophilic gastroenteritis4) Lactose intolerance5) Milk protein enterocolitis
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Facts to know• IgE milk allergies usually begin in the 1st year of life-
hives , AD, & anaphylaxis within minutes to an hr of ingestion
• Milk protein enteropathies usually present within the 1st year of life with hematochezia, diarrhea, & vomiting
• Oral allergy is due to fruits & is associated with pollen allergies
• EE we’ll talk about later• Lactase deficiencies usually present after 6 yrs of
age- bloating
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An 8 yr old presents with fever, arthralgia, arthritis and urticaria 3 days after completing a course of amoxicillin for strep throat. The most likely diagnosis is:
• A) erythema multiforme• B) IgE mediated pcn allergy• C) post streptococcal arthritis• D) serum sickness • E) delayed PCN allergy
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Facts to know
• EM classically have target lesions• IgE mediated medication reactions usually
start within a few days after initiating therapy• Serum sickness is type III reaction that begins
1-2 wks (up to 20 days) from initiating therapy. Fever, rash, malaise, lymphadenopathy, arthralgia & arthritis
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A 7 year old girl had a history of URI symptoms & fever 2 weeks ago and was given OTC medications. She also ingested broccoli for the first time. She has had this rash for 2 weeks.
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The most likely cause of this rash is
• A) a viral infection• B) a dye in her OTC medication• C) ibuprofen• D) Lyme disease• E) allergy to broccoli
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Etiology of Hives• Foods- children- peanuts, nuts, fish, shellfish
infants-milk, eggs, wheat, soy (contamination commonly happens at restaurants)
• Medications - penicillin & derivatives, cephalosporins, tetracycline, sulfonamides, insulin, ibuprofen
• Viral infections can last weeks as opposed to foods• Physical urticarias- dermographism, pressure, cold, heat,
solar, exercise, vibratory• Idiopathic• Medical conditions are unlikely to trigger hives in the
pediatric population
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A ten year old presents with recurrent angioedema of the extremities and at times his throat. His past medical history is significant for surgery to R/O appendicitis but no clear diagnosis was made. The family Hx is significant for a father with a peanut and PCN allergy. The most appropriate test to perform is:
A. Peanut RastB. C4 levelC. Skin testing for PCND. SPEPE. C1 level
30Pean
ut Rast
C4 level
Skin te
sting fo
r PCN
SPEP
C1 level
0% 0% 0%0%0%
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Hereditary Angioneurotic Edema (HAE)• Patients do not have Hives with attacks• Usually present from 3-20 years of age• Often is discovered after the patient presents with
symptoms of appendicitis• C1 esterase inhibitor is deficient causing increase in
kinins and edema• C4 is almost always low, C2 is low during attacks• C1 esterase inhibitor levels are low but there is a
version with normal levels but abnormal functioning• Treatment with C1 esterase inhibitor and other
therapies are now available31
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A 13 yr old presents with hives for 6 months. He had Immunocap testing performed which was positive for dust mites, milk and shrimp. The hives last 3-5 hours, then disappear. The most likely cause of the hives is…
A) autoimmune thyroid diseaseB) allergies to dustC) allergies to foodD) mastocytosisE) autoantibodies to the IgE receptor
32A) auto
immune th
yroid ...
B) alle
rgies t
o dust
C) alle
rgies t
o food
D) masto
cyto
sis
E) auto
antibodies to th
e ...
0% 0% 0%0%0%
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Facts to know• Chronic urticaria is defined by hives lasting more
than 6 weeks. It is rarely caused by foods or inhalants. Positive Immunocap testing usually means very little with hives unless there is a clear history suggesting a cause.
• Routine Immunocap testing for chronic hives is not indicated.
• CU in 40% of patients is caused by autoantibodies to the IgE Fc epsilon 1 receptor
• Thyroid antibodies are associated with CU but is not the cause
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A 4 yr old presents with sneezing and rhinorrhea lasting 4 days. The discharge is from one nostril, foul smelling and is described as blood tinged.
The most likely diagnosis isA) Allergic rhinitisB) SinusitisC) Nasal foreign bodyD) Nasal polypsE) Viral rhinitis 34
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A three year old presents with recurrent respiratory infections, chronic rhinitis that is bilateral & year round. Your examination of the nose reveals these pictures.
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Continued
• The most likely diagnosis is
• A) granuloma• B) cystic fibrosis• C) deviated septum• D) foreign body• E) Brutons agammaglobulinemia
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A 7 year old presents with a 3 year history of seasonal rhinorrhea and congestion. His symptoms begin each spring. On PE you note pale boggy turbinates and a transverse nasal crease.
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The most effective long term treatment is a nasal spray containing a
• A) corticosteroid• B) anticholinergic• C) decongestant• D) mast cell stabilizer• E) saline solution
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• Topical nasal steroids are the most potent treatment for allergic rhinitis
• Anticholinergic nasal sprays may help for vasomotor rhinitis/non allergic rhinitis
• Mast cell stabilizers must be used several times a day for many days before it starts working
• Nasal decongestant can cause a rebound effect when used more than 5 days
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Signs and Symptoms ofAllergic Rhinitis
Skoner DP. J Allergy Clin Immunol. 2001;108:S2-S8.
• Sneezing• Itchy nose, eyes, throat,
and/or ears• Nasal congestion• Clear rhinorrhea
• Conjunctival edema, itching, tearing, hyperemia
• Subocular edema and darkening (“shiners”)
• Loss of taste and smell sensations• Diagnosis depends on a thorough
patient history regarding symptoms suffered, seasonal and/or perennial patterns of symptoms, and symptom triggers
• Diagnosis is confirmed by allergy skin testing or RAST
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Differential Dx of RhinitisDiagnosis Symptoms• Vasomotor rhinitis congestion, rhinorrhea • Anatomical
– Adenoidal hypertrophy comgestion, snoring– Deviated septum– Polyps must R/O CF– Foreign body unilateral, bloody or brown
discharge
• Infectious – Viral clear rhinorrhea– sinusitis mucopurulent discharge,
cough, facial pain, tooth pain
( Most common symptom of chronic sinusitis is chronic cough) 41
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Differential Dx 2
Diagnosis Symptoms• Hormonal congestion
– Pregnancy, hypothyroidism• CSF fluid –cribiform plate Fx , clear rhinorrhea
– MVA• Rhinitis medicamentosa congestion
rhinorrhea– Beta blockers, cocaine – OTC nasal sprays (AFRIN) rebound congestion
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A 6 year old boy has increased symptoms of asthma each fall when school begins. He also experiences rhinorrhea, congestion and ocular symptoms during this time.
• The most likely trigger to his symptoms are• A) sinusitis• B) GE reflux• C) viral infections• D) allergic rhinitis• E) school stress
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What allergens trigger Rhinitis & Asthma?
• Indoor allergens (cause year round symptoms)– Dust mites (avoidance measures)– Mold– Cockroaches– Pets –cats, dogs, rats, mice, guinea pigs, & birds
• Outdoor allergens (cause seasonal symptoms)– Pollen – trees grass weeds– Molds– Animals – horses, cows
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Asthma Triggers• Eighty percent of children with asthma develop allergic
rhinitis, a known trigger to asthma• GER exacerbates asthma and can be silent. Most infants
will have frequent spitting up or vomiting. Older children can complain of heartburn
• School stress can result in a psychogenic cough (disappears when sleeping)
• Sinusitis also exacerbates asthma and would be suspected with a purulent discharge
• URI’s are the most common trigger in infants• Exercise in the school age child triggers symptoms in most
asthmatics
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The risk factor most associated with fatal asthma is
• A) Poor perception of asthma• B) high socioeconomic status• C) female• D) sinusitis• E) Inhaled steroid use
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• Risk factors for near fatal and fatal asthma include frequent visits to the ER, hospitalizations, psychosocial disturbances, male sex, poor perception of hypoxia, low socioeconomic status, over use of beta agonists
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The mother of a 10 yr old complains of her sons asthma worsening during the spring months during his outdoor basketball season. He has no symptoms during winter months and he does play football then. The best advice for the mother is to:
• A) have skin testing performed• B) order a methacholine challenge• C) perform an exercise challenge• D) stop basketball and continue football• E) start the child on salmeterol 48
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An allergic inner city 10 year old child has perennial rhinitis and asthma. The most common allergen responsible for this inner city asthmatic is• A) Cockroach• B) Cat dander• C) Dust mites• D) Mouse urine• E) House dust
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• 2 month old boy presents with blood in the stools. Started 3 weeks ago. FT, NSVD, no complications. Breastfeeding since birth with supplementation. Initially on cow’s milk formula, but switched to soy-based formula when blood was noticed in the stool. Symptoms continued so switched to extensively hydrolyzed formula.
• What is the diagnosis?• What is the management?
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Dietary protein induced proctocolitis syndrome
• Affects children in first few months of life• Symptoms: blood streaks mixed with mucus in
stools, no systemic symptoms – - Minimal blood loss, anemia is rare
• Milk is the most common cause, soy can be another trigger (50% of milk allergic pts are also soy allergic)
• Non IgE mediated reaction• Tx –Avoidance- Most outgrow the allergy between 1-
2 yrs Sicherer, Pediatrics 2003
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The following is true concerning food allergies:
A) The AAP recommends allergic infants be breastfed or given a hydrolyzed formula for the first 6 months of life
B) The AAP recommends delaying peanut exposure until 2 years of age
C) The AAP recommends delaying peanut exposure until 3 years of age
D) The AAP recommends mothers avoid allergic foods while pregnant
E) The AAP recommends mothers avoid allergic foods while nursing
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A child has a history of sevre anaphylaxis to eggs. The mother does not want her child to receive the MMR vaccine. The most appropriate course of action is to:
• A) Refer the family to an allergist for administration of the vaccine
• B) defer administration of the vaccine• C) have the child tested directly to the vaccine• D) administer the vaccine and observe in your
office for 1 hour• E) administer the vaccine and let her go home53
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A 5 yr old has a hx of a peanut allergy. Skin prick testing confirmed the allergy. The mother asked about the child’s risk of other food allergies. The food most likely to cause an allergic reaction is
• A) wheat• B) beans• C) shrimp• D) fish• E) tree nuts
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Facts to know• Children with peanut and nut allergies are unlikely
to outgrow their allergy• There are no approved therapies to tx peanut and
nut allergies• There are centers that are experimenting with oral
immunotherpy and other therapies• Baked milk and eggs given to milk and egg allergic
pts respectively, can help outgrow these allergies• There is cross reactivity with tree nuts and peanuts
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A 1 yr old has a Hx of severe gastroesophageal reflux that failed tx with multiple medications. She had a Nissen fundoplication and continues to reflux. Biopsy of the esophagus showed eosinophils. The following is true except:
A. There should be greater than 15 eosinophils per high power field on the biopsy
B. Exclusive feeding with an amino based formula usually resolves the problem
C. Inhaled steroids that are swallowed helps this condition
D. The most common food that causes this condition is soy
E. Antihistamines in general don’t work for this condition
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When to consider an immunodeficiency
Unusual infections (recurrent and severe) – abscess, pneumonia, sinusitis, thrushUnusual bugsAntibiotics don’t help, need IV antibioticsFailure to thriveFamily history of immunodeficiency
What is a normal number of infections? Usually 6-8 colds per yearChildren attending daycare or have siblings in school tend to have more than othersNot unusual to have 6 otitis or 2 gastroenteritis in first few years 57
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The Immune System
• T cells• B cells (that make immunoglobulins)• Phagocytic system (neutrophils and
macrophages)• Complement
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A 5 yr old is admitted to the hospital with his 4th pneumonia. He has a history of recurrent OM and sinusitis diagnosed by CT scan. His heart sounds are heard better on the left side of the chest. The best test to confirm his diagnosis is:
A) serum immunoglobulinsB) T cell subsetsC) a sweat testD) CH 50E) ciliary biopsy
59A) seru
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Primary Ciliary Dykinesia (inmmootile cylia syndrome)
(Kartagener syndrome)• Present with recurrent om, sinusitis and
pneumonia• Situs inversus• Nasal polyps• Bronchiectasis (Tram track lines on CTscan)• Dx made with ciliary biopsy
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A 2 year old presents with recurrent bacterial and viral infections. The most appropriate initial tests to be performed are:
• A) immunoglobulin subsets• B) candida and tetanus skin tests• C) B & T cell subsets• D) complement 50 assay• E) CBC and immunoglobulins
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A 16 yr old is admitted with fever, headache, lethargy nuchal rigidity and a petechial rash. He was diagnosed with Neisseria Meningitides twice in the past. The best test to perform to make the DX is:
• 1) CH 50• 2) serum immunoglobulins• 3) Immunoglobulin subsets• 4) HIV test• 5) T cell stimulation test
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Primary Immune System DefectsPresent With
• T cells – viral & fungal infections• B cells – recurrent bacterial infections• Phagocytic system- cellulitis, skin abscesses,
pneumonia, periodontal disease • Complement- c5-9 Neisserial infections
C1,2 & 4 -recurrent bacterial infections & SLE
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Work up of Immunodeficiencies
• 70% of Immunodeficiency syndromes have immunoglobulins that are abnormal
• CBC with differential allows us to look at neutrophil & lymphcyte count, and platelets
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B cell Work Up
• CBC with diff• Quantitative Immunoglobulins • Pre & Post vaccination titers• Isohemmaglutinin testing (antibodies to AB
blood antigens)
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Work up of Immunodeficiencies
• T cell- Cell mediated immunity – delayed type hypersensitivity intradermal skin test candida, tetanus, mumps, trichophyton. Other measures include lymphocyte count, T cell subpopulations by flow cytometry and lymphocyte stimulation tests
• Dihydrorhomadine flourescence (DHR 123) measure neutrophil respiratory burst and is replacing the NBT test that diagnoses Chronic Granulomatous disease
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Work up of Immunodeficiencies
• Complement deficiencies only make up 2% of primary immunodeficiencies
• Total Complement assay ( complement 50 or CH 50) measures the intactness of the classic complement pathway. Deficiencies from C1 through C9 can be picked up with this test
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A 14 month old presents with severe eczema, recurrent otitis, Strep Pneumo pneumonias. Blood tests reveal thrombocytopenia and small platelets
The most likely diagnosis is:• A) X linked severe combined
immunodeficiency• B) DiGeorge syndrome• C) Wiskott-Aldrich syndrome• D) Chronic granulomatous disease• E) Brutons X linked agammaglobulinemia 68
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Wiskott-Aldrich syndrome
• Prolonged bleeding after circumcision, bloody diarrhea
• Recurrent infections and significant eczema that begin prior to 1 year of age
• Small platelets and Thrombocytopenia• Treatment- IV gammaglobulin, prophylactic
antibiotics, Identical bone marrow transplant
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Brutons X linked agammaglobulinemia
• Defect in the B cell tyrosine kinase protein• Decrease in B cells production• Severe hypogammaglobulinemia• Small or absent tonsils• Sinopulmonary infections after 6 months of
age• Tx – IVIG
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CVID -Common variable immunodeficiency
Similar presentation to Brutons (sinopulmonary infections) but occurs in the older child or adult
Not as severe hypogammaglobulinemia as Brutons
Diarrhea due to Giardia Normal B cells Tx -IVIG
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Chronic Granulomatous Disease (CGD)
• Disorder of phagocytic system• Inability to kill catalase positive organisms (Staph
aureus, Serratia, Burkholderia cepacia, Salmonella, Aspergillus, & Candida)
• Recurrent lymphadenitis, skin infections, hepatic abscesses & osteomyelitis
• Tx- Cure – bone marrow transplant– Supportive care- interferon gamma and prophylactic
antibioticsDiagnosis DHR 123 or NBT test
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DiGeorge Syndrome• Genetic disorder linked to chromosome 22 q11.2 &
dysmorphogenesis of the 3rd and 4th pharyngael pouches
• Can have a partial or complete DiGeorge• Can present in infancy with hypocalcemic tetany• Aortic arch and cardiac defects• Hypoplastic mandible, defective ears, and a short
philtrum, absent thymus• Recurrent viral, bacterial and fungal infections• Tx- Bone marrow or thymic transplant
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Ataxia Telangiectasia
• Telangiectsis of conjuntivae and skin• Cerebellar degeneration and ataxia• Dysarthria, nystagmus, choreoathetosis• Recurrent sinus, ear, and pulmonary
infections• Decrease in IgA & IgE• Low lymphocyte count with poor mitogen
stimulation response• Abnormal delayed type hypersensitivity
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SCID (severe combined immunodeficiency) T and B cells defects
• Onset in early life• Medical emergency• Recurrent sepsis, pneumonia, otitis, rash, diarrhea• Opportunistic infections – PCP, Candida• FTT when infections begin• Severe lymphopenia – no lymphoid tissue, no thymus• Death by age 2 years• Treatment: stem cell transplant• Many different mutations
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Transient Hypogammaglobulinemia of Infancy• All children need several years for
immunologlobulins levels and antibody responses to become normal
• Small number of children with recurrent infections have been found to have low immunoglobulin levels that eventually normalize
• Have ability to form specific antibodies in response to immunizations
• Have normal immunoglobulin levels by 2-4 years• Need to compare levels based on age – some lab
reference ranges are adult levels
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Leukocyte adhesion defect (LAD)
• Delayed separation of umbilical cord• Elevated WBC count• Recurrent necrotic infections of skin, mucous
membranes, GI tract
• 2 types• LAD-1 – defect or deficiency in CD18• LAD-2 – defect in fucose metabolism (rare)
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