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Disclosures Dr. Brooks Advisory board, research grant ‐ United Allergy Services speaker’s bureau ‐ Merck
Edward G. Brooks, MD Pediatrics Grand Rounds Sept 5, 2014
Learning Objectives Differential diagnosis of hypersensitivity disorders Management of hypersensitivity
Case #1 5 y/o boy with 3 month history of nasal congestion,
nighttime cough, bad breath, intermittant purulent rhinnorhea alternating with clear rhinnorhea, episodes of sneezing/nasal itching OTC cold meds haven’t worked This has been recurrent for the past 2 years Possible diagnoses?
Bacterial sinusitis vs Allergic Rhinitis
Allergic Rhinitis: signs and symptoms Since this is not a board test you get to ask additional
questions: number and duration of antibiotic courses last time child was completely clear allergic triggers family Hx. sinus/allergic disease seasonality of symptoms exposures (siblings, school, allergens, pollutants, etc.) breathing problems (asthma, CF) other infections (immunodeficiency) foul discharge from nare unilaterally (foreign body)
Provoked by exposure to environmental allergens Common Symptoms: – Nasal, eye itching – Sneezing, clear rhinorrhea, post nasal drip, watery eyes tearing – Mouth breathing, sleep disturbances - Mucosal edema with nasal congestion / obstruction – “Sinus” headache, ear pressure - ostial & eustachian tube dysfunction – Reduced taste and smell olfactory dysfunction
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Allergic Rhinitis:
Allergic Rhinitis:
signs and symptoms
signs and symptoms
Eyes: – conjunctivitis, Dennie’s lines, allergic “shiners” Nose: – edematous/pale/enlarged nasal turbinates, clear/thin mucoid rhinitis, polyps, transverse nasal crease from “allergic salute” Ears: – otitis media, retracted tympanic membrane from ET dysfunction Throat: – prominent lymphoid patches (cobblestoning) lateral pharyngeal bands
Allergic conjunctivitis
allergic shiners
Eyes: – conjunctivitis, Dennie’s lines, allergic “shiners” Nose: – edematous/pale/enlarged nasal turbinates, clear/thin mucoid rhinitis, polyps, transverse nasal crease from the “allergic salute” Ears: – otitis media, retracted tympanic membrane from ET dysfunction Throat: – prominent lymphoid patches (cobblestoning), lateral pharyngeal bands
Allergic crease
Allergic Rhinitis ‐ triggers
Allergic Rhinitis: signs and symptoms
Eyes: – conjunctivitis, Dennie’s lines, allergic “shiners” Nose: – edematous/pale/enlarged nasal turbinates, clear/thin mucoid rhinitis, polyps, transverse nasal crease from the “allergic salute” Ears: – otitis media, retracted tympanic membrane from ET dysfunction Throat: – prominent lymphoid patches (cobblestoning), lateral pharyngeal bands
Allergic crease
Allergic salute
Provoked by exposure to environmental allergens Perennial (year round) (mites, molds, pets) Seasonal (intermittent) (pollens)
Allergic salute
Is it allergy or a URI?
Treatment of Allergic Rhinitis
% of Patients with Symptom Avoidance – allergens and irritants (smoke, chemicals) Antihistamines - (pruritis, rhinorrhea) Corticosteroids-topical (all symptoms) Leukotriene Receptor Antagonists (congestion) Decongestants-topical or systemic (congestion)
70
Sore Throat
50
Cough
40
Nasal Drainage
Anticholinergics
30
Cromolyn (congestion)
20
Allergen Immunotherapy (desensitization)
Fever
60
10 0
1
2
3
4
5
6
7
8
9
10
11 12 13 14
Day of Illness
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Acute Bacterial Rhinosinusitis
Most Rhinosinusitis Results From a Cycle of Mucosal Inflammation Mucosal Swelling (URI, allergy, environment)
• Most often preceded by a viral URI • A [probable] diagnosis may be made if a viral URI has not improved after 10 days or has worsened after 5 to 7 days or if symptoms are out of proportion to a typical URI • Common bacteria: - Streptococcus pneumoniae -
Hemophilus influenzae
-
Moraxella catarrhalis
-
Staphylococcus aureus, atypical bacteria (M. pneumoniae)
Bacterial Infection
Ostial Obstruction
Mucous Stasis (antihistamines)
Atopic disease Asthma, Allergic Rhinitis, Food allergy, Eczema
The Atopic March In utero Genetic predisposition Maternal influence-fetal programming Environmental factors
Infancy Eczema Food Allergy
Toddler Asthma
School Age Asthma Allergic rhinitis
Cells of Allergic Inflammation
Allergic Sensitization
Antigen Presenting Cell B Cell
IL-4 IL-13 IL-3 IL-4 IL-6 IL-9 IL-13
TH2 Cell IL-3 IL-5 GM-CSF Eotaxin TNF- IL-4
IgE Mast Cell
VCAM
ICAM
Vascular Endothelium
Eosinophil Neutrophil
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Case #2
Late Phase Reaction in Nasal Mucosa
18 month male with episode of facial swelling after eating peanut butter.
The late phase of the Type I hypersensitivity
Infiltration of inflammatory cells, especially eosinophils, lymphocytes
At age 3 y/o developed welts after touching peanuts. What’s he allergic to? Do you really need a test to tell you this? What’s the treatment? What do you tell the family?
At 5 y/o he developed acute urticaria over the eye when a classmate threw a peanut butter and jelly sandwich at him. At age 6 y/o, developed throat tightness when he ate a chocolate chip cookie at school. Upon closer inspection of the package, it read… “May contain peanuts and/or tree nuts”
But what if the story was “ He went to a school party, and we have no idea what he ate?” What do you do?
Specific IgE Testing Skin Prick Testing
ImmunoCap
In‐Vitro testing
Positive = 3 mm wheal > negative control Good negative predictive value ~ 50% false positive
Case #3
Major Food Allergens
USA: Milk Egg Peanuts Tree nuts Seafood
Israel: Egg Milk Sesame seeds
What’s the diagnosis?
Anaphylaxis Singapore: Birdsnest Seafood Egg Milk
Treatment?
Rx: epinephrine and anti-histamines Had 2 more episodes after eating chocolate syrup at a restaurant and after exposure to hand sanitizer on the school bus What’s the allergen?
France: Egg Peanuts Italy: Milk Milk Mustard Egg Seafood Sampson et al.
10 yo girl had 3 episodes of lip and tongue swelling, throat tightness, dyspnea after putting Neosporin on her lips, after eating Raman noodles and after eating chicken nuggets.
Australia: Milk Egg Peanuts Sesame seeds
Allergy testing for common food, insect and inhalant allergens was negative. Common ingredient: Methylparaben Common preservative used in just about EVERYTHING! Also occurs naturally in fruits (blueberries)
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Anaphylaxis definition(s): 1) the acute onset of a reaction (minutes to hours) with involvement of the skin, mucosal tissue or both and at least one of the following: a) respiratory compromise or b) reduced blood pressure or symptoms of end-organ dysfunction 2) two or more of the following that occur rapidly after exposure to a likely allergen for that patient – involvement of the skin/mucosal tissue, respiratory compromise, reduced blood pressure or associated symptoms and/or persistent gastrointestinal symptoms 3) reduced blood pressure after exposure to a known allergen The diagnosis and management of anaphylaxis practice parameter: 2010 Update. JACI 2010
Urticaria
Angioedema
Angioedema Laryngeal edema
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Case #4 12 yo boy with well-controlled asthma was traveling from Midland to San Antonio. During the trip he developed a slight rash and wheezing not responsive to his rescue inhaler. Family drove straight to the ER.
Insect Stings Imported fire ants stings are a common
etiology for occult anaphylaxis
Dx: asthma exacerbation Rx: steroids and albuterol
Anaphylaxis in 1% of children stung
No precipitating factors were identified, no URI sx, no new meds, no toxic exposures. He had various snacks during the trip, but had no h/o food allergy.
Symptoms usually occur within minutes Local reactions do not predict a severe
What triggered his asthma?
reaction; large local reactions/systemic are associated with slight increased risk Immunotherapy very effective
Cutaneous local reactions very common Systemic reaction in 5-10%
Food allergy testing was negative Testing to imported fire ants positive
Anaphylaxis testing Serum tryptase – levels peak 60-90 min.
after onset and persist for 6 hours, special handling 24 hour Urinary methyl-histamine IgE testing – 6 weeks after event Challenge testing
Emergency treatment of anaphylaxis Epinephrine (0.01 cc/kg of 1:1000) 0.3 cc (>30 kg, ~ 9 y/o ), 0.15 cc (15-30 kg) Anti-histamines – primarily short acting H1 antagonists (diphenhydranmine) Corticosteroids – beneficial in asthma sx, and to prevent late-phase reactions Remain recumbent if hypotension present (fluid resuscitation) Observe for 4-8 hours
Indications for Extended Observation • Severe reaction of slow onset • History of previous biphasic reaction • Marked asthmatic component • Ingested antigen (continuous absorption)
Discharge
Lieberman et al. The diagnosis and management of anaphylaxis practice parameter: 2010 Update. J Alllergy Clin Immunol. 2010; 126(3):477.
Autoinjectable epinephrine Anti-histamines for 24-48 hours Corticosteroids for 24-48 hours Education: avoidance of suspected causative agents F/U allergy eval.
Case #5
Allergic Food Disorders
8 yo girl evaluated for FTT and multiple food allergies
IgE-Mediated PMHx: began vomiting with breast feeding, placed on elemental formula. Had vomiting, GERD, diarrhea, abdominal pain to multiple other foods. Esophageal bx demonstrated >25 Eos/HPF IgE testing showed multiple reactions (lemon > 50 kU/L,