pediatric allergology_dr. t. tolentino (2)
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PEDIATRIC ALLERGOLOGY
Allergy
Coined by Von Pirquet in 1906o Allos: othero Ergon: work
When a substance which is not harmful in itself causes anexaggerated or inappropriate immune response in
predisposed individuals
Allergy and Atopy
Not interchangeable terms Allergy
o Refers to hypersensitivity that occurs upon re-exposure to the sensitizing allergen, causing the
release of inflammatory mediators
Atopyo Refers to an individual being prone to develop
allergies because of a genetic state of
hyperresponsiveness to allergens associated
with:
Asthma Allergic rhinitis Atopic dermatitis
Type I Allergic Reaction
Plasma cellIgEbecomes attached to a surface ofmast cell or basophilencounters an antigenrelease
of chemical mediators
Sensitization phaseo Plasma cell IgE
Effector phaseo Early phaseo Late phase
Sensitization Phase
Effector Phase
Systemic manifestationso Conjunctivitiso Angioedemao Allergic rhinitiso Anaphylactic laryngeal edemao Asthmao GI symptomso Urticariao Intestinal edema (diarrhea)o Angioedema
Atopic Dermatitiso Between Type I and Type IV
Urticaria
Angioedema
Allergic rhinitiso Allergic shinerso Mouth breathero Facial grimaceo Allergic hand salute
Type II Allergic Reaction
Cell bound antigenantigen-antibody complex complement acts into antigen-antibody complex lysis of
cell
Primarily because of the action of complement
Type III Allergic Reaction
Antigen complex on vessel wallcomplement cascade neutrophil attractionantigen-antibody complex will be
phagocytisedenzyme releaseinflammatory changes
such as vasculitis
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Type IV Allergic Reaction
Basic cell: T lymphocytesantigen presented to Tlymphocyteschemotactic factors antigen are
phagocytizedenzyme release
o Increased permeabilityo Slow inflammationo Raised lesion
Cellular Interaction, Cytokines, and Immune Regulation
TH0 (Ag + MHC)o IL3, IL4, IL5, IL9TH2
IgE reaction Prasitic infection Eosinophilic infiltration
o IFN-y, IL2, IL10TH1 Cytotoxic/delayed type
hypersensitivity
Viral infection Intracellular pathogens
Chemical Mediators
Type of cell generating the mediatorso Primary
Preformed Newly formed
o Secondary Eosinophils Cytokines More potent and with heavier weight Actions are longer Mediate greater inflammation
Allergic Inflammatory Response
Allergen provocation in the airways and skin results in abiphasic response
Early phaseo Starts within minutes and subsides in 1-2 hourso Reaction due to primary mediators
Histamine Leukotrienes PAF (Platelet activating Factor)
o Inhibited by antihistamines and mast cellstabilizers
Late Phaseo
Starts after 2-4 hours and terminates in 24-48hours
o Characterized by cellular infiltrateso Reaction due to second round of mediator
release
o Inhibited by glucocorticoids *pic: Skin test (Immediate and Late Phase)
TH0
Ag + MHCIL3
IL4
IL5
IL9
IFN-y
IL2
IL10
TH2 TH1
IgE reaction
Parasitic Infection
Eosino hilic infiltration
Cytotoxic/Delayed type
hypersensitivity
Viral infection
Intracellular pathogens
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Isaac Study
Prevalence of Diagnosed Atopic Dermatitiso 6-7 years: 4.3%o 13-14%: 7.1%o Present: increasing incidence
Prevalence of Diagnosed Asthmao 6-7 years: 16.4%o 13-14 years: 17.6%
Prevalence of Diagnosed Allergic rhinitiso 6-7 years: 26.2%o 13-14 years: 32.5%
A strict relationship between allergic rhinitis and allergicasthma has been seen recently, and in many ways
respiratory allergy could be seen as a single disorder of the
airways
Atopic dermatitis and Food allergy have been linked with anincreased risk of evolving into a more serious allergic disease
such as asthma
History
Symptoms Fully explore the types of symptoms and when and how
often they occur
Exacerbating/alleviating factors
What makes the symptoms worse? What makes them better? Does exposure to pets, smoke, perfume, or a change in air
temperature affect them?
Are certain seasons better than others? History of drug exposure, temporal relationship
Environmental
Critical in determining occupational allergen exposures Where does the patient live, work, play? What exposures are present in each of these environment? Does the patient have a pet Does the pet have access to the patients bedroom? Nearby vacant lots, trees, factories, fields
Family history
Allergic diseases have a strong hereditary link Important to ask if there are other family members with
allergic diseases
o 1 parent with allergic disease: 40% chance ofhaving allergies
o 2 parents with allergic disease: 60-80% chance ofhaving allergies
Genetic Basis for Atopy
o ~60% heritability in twin studies of asthma andatopic dermatitis
o 5q23-35 region Genes for TH2 cytokines IL3, IL4, IL5, IL9, IL13, GM-CSF
Psychosocial issues
Often a failed interaction with a patient results fromunanticipated or identified psychosocial barrier
Allergy Overview
Host and Environmental Factors in the Development of Allergic
Disease
Allergy is the contribution primarily of genes, with theinteraction with environment, presence of cytokine
dysregulation and timing of its expression
T Helper lymphocyte differentiation to Th1 or Th2
Novel concept of a regulatory T cell (Treg) which functions tobalance the expression of TH1 and TH2 cytokine expression
Development of Atopic Disease
Allergic Marcho Aka Atopic Marcho Typical evolution of allergic diseaseso At birth
Upsurge of food allergyo Then atopic dermatitiso As patient grows older: waneso School-aged: upsurge of respiratory allergies
Nave Th
TH2
TH1
Treg
IL4, IL5, IL13
(Pro-allergic)
IFN-y, IL2
(Anti-allergic)
IL4
IL12, IL18
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Pathophysiology
First allergen exposure antigen presenting cell B cellPlasma cellIgEmast cellsecond exposure to
allergenmast cell degranulationallergic symptoms
Adverse Food reactions
Non-immunologic
Toxico Scombroid poisoning
Eating seafoods that are not fresh Symptoms of diarrhea or anaphylaxis Due to a toxins released by the stale
seafood
o Bacterial/food poisoningo Heavy metal poisoningo Caffeineo Alcoholo Histamine
Non-toxic/Intoleranceo Galactosemiaso Lactose intoleranceo Pancreatic insufficiencyo Gallbladder/Liver diseaseo Hiatal herniao Gustatory rhinitiso Anorexia nervosa
Most common food allergens in our settingo Milko Shellfisho Eggo Fisho Wheato
Soyo Rice
Immunologic (types I-IV)
Immunologic Spectrumo IgE mediated
Oral allergy syndrome Confined to oral and
pharyngeal area only
Redness Angioedema Due to ingestion of fresh
fruits and vegetables
Anaphylaxis
Only emergency inallergology
Urticariao Mid-way between IgE mediated and non-IgE
mediated
Esoinophilic esophagitis Eosinophilic gastritis Eosinophilic gastroenteritis Atopic dermatitis
o Non-IgE mediated Protein induced enterocolitis Protein induced enteropathy Eosinophilic proctitis
Due to cows milk, soy Dermatitis herpetiformis
Sometimes outgrown
Eggs Milk Soy
Usually not outgrown
Peanuts Tree nuts Fish Shell fish
Atopic Dermatitis
Most common chronic inflammatory skin disease inchildhood
Characterized by itch and frequent skin infections Affected individuals with moderate-severe disease often
have disruption of sleep, daily activities, school, work
Epidemiology and Natural History
Worldwide: 10-20% 80% have onset before 5 years old Most (60%), especially those with mild Atopic Dermatitis,
outgrow it by adolescence Patients with moderate-severe Atopic Dermatitis have
persistent disease into their adulthood
A significant portion of atopic dermatitis children are at riskfor developing allergic rhinitis and Bronchial asthma
Pathogenesis
Genetics play an important role Various genetic polymorphism involving skin barrier defects
and immune functions have been associated with Atopic
Dermatitis
o Genetic variation in epidermal differentiationcomplex (EDC)
o Filaggrin gene loss of function mutations Role of Staphylococcus aureus as an inducer of inflammation
via the effect of superantigen and superantigen-specific IgE
Hanifin and Rajka Criteria
Major criteriao Prurituso Morphology and distribution
Facial and extensor involvement ininfants and children
Flexural lichenification in adultso Chronically-relapsing dermatitiso Personal or family history of atopic disease
Minor criteriao Anterior neck foldso Xerosiso Keratosis pilaris
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o Dennie-Morgan foldso Facial pallor/erythemao Pityriasis albao Itch when sweatingo Cutaneous infectionso Nipple eczemao Orbital darkeningo Palmar hyperlinearityo White dermatographismo (+) immediate type allergy skin testso Elevated serum IgE
Management of Atopic Dermatitis
Evaluation of severity: validated scoring systemso SCORADo EASI
Routine daily skin care Topical steroids and calcineurin blockers Management of itch and sleep
Scoring of Atopic Dermatitis (SCORAD)
Used to assess the extent and severity of eczema Parameters
o Extent of eczema To determine extent, the sites
affected by eczema are shaded
The rule of 9 is used to calculated theaffected are as a percentage of the
whole body
o Intensity of eczema A representative area of eczema is
selected
In this area, the intensity of each ofthe following signs is assessed as:
None: 0 Mild: 1 Moderate: 2 Severe: 3
Signs Redness Swelling Oozing/crusting Skin thickening
(Lichenification)
Drynesso This is assessed
in an area
where there is
no inflammation
The intensity scores are addedtogether
o Degree of itching and Sleep Disturbance Scored by the patient using a visual
analogue scale where 0 is no itch or
sleeplessness and 10 is the worstimaginable itch or sleeplessness
Eczema Area and Severity Index (EASI)
Used to measure the severity and extent of Atopic eczema The intensity of a representative area of eczema and the
approximate percentage affected by eczema are calculated
for each region
o Head and necko Upper limbso Trunko Lower limbso Parameters
Redness Thickness
Induration Population Edema
Scratching Excoriation
Lichenificationo Scoring
None: 0 Mild: 1 Moderate: 2 Severe: 3 Half scores are allowed
o The four intensity scores are added up for each ofthe four body regions to give subtotals A1, A2,
A3, A4. Each subtotal is multiplied by the body
surface area represented by that region
A1 x 0.1 gives B1 A2 x 0.2 gives B2 A3 x 0.3 gives B3 A4 x 0.4 gives B4
The percentage area affected by eczema is evaluated in thefour regions of the body. In each region, the area is
expressed as:
o None: 0o 1-9%: 1o 10-29%: 2
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o 30-49%: 3o 50-69%: 4o 70-89%: 5o 90-100%: 6
Each of the body area scores is multiplied by the areaaffected
o B1 x (area score) = C1o B2 x (area score) = C2o B3 x (area score) = C3o B4 x (area score) = C4
The total EASI score is C1 + C2 + C3 + C4
Allergic Rhinitis
Clinical definition
Symptomatic disorder of the nose induced by an IgE-mediated inflammatory reaction after allergen exposures of
the membranes lining the nose
Symptoms
Rhinorrhea Nasal congestion Sneezing Nasal pruritus Post-nasal drainage Other symptoms
o Fatigueo Headacheo Disrupted sleep patternso Decline in cognitive processing
Epidemiology
Prevalenceo 15-20% worldwide but physician-diagnosed
Allergic rhinitis in children is around 42%
1997 survey: 16.9 M clinic visits 2000 survey: $6B spent on prescription and OTC medications
for allergic rhinitis
Hidden direct costs include asthma treatment, URTI,sinusitis, otitis media, nasal polyposis, and obstructive sleepapnea
Allergic Rhinitis and its Impact on Asthma
The theory of One Airway, One Disease led to thedevelopment of ARIA in 1999
Based on the primary prevention of asthma through themanagement of allergic rhinitis
New international standard for the Classification andStepwise Management of Allergic Rhinitis
The ARIA Guideline reclassifies Allergic rhinitis on the basisof duration of symptoms and quality of life outcomes
o Replaces the current nomenclature of seasonaland perennial rhinitis
ARIA Classification of Allergic Rhinitiso Intermittent symptoms
4 consecutive
weeks
o Mild All of the following
Normal sleep No impairment of daily
activities, sport, leisure
No impairment of school orwork
Symptoms present but nottroublesome
o Moderate-Severe One or more items
Sleep disturbance Impairment of daily
activities, sport, leisure
Impairment of school orwork
Troublesome symptoms
Stepwise Treatment of Allergic Rhinitis
o Intranasal steroid is the most effectivepharmacologic treatment for Allergic rhinitis
o Mainstays of treatment
Intranasal steroids Anti-histamine Anti-leukotriene
ARIA algorithm
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Important Points in the treatment of Allergic Rhinitis
Medications may be given singly or in combination There is no preferred order except in moderate-severe
persistent allergic rhinitis wherein Intranasal steroid is the
first choice
Used for at least 2 weeks Patients are re-evaluated Medications are adjusted on the basis of response to
treatment
If there is improvement, medications are continued for atleast 1 month
o Thus, 2 months is the minimum duration oftreatment
Allergic Rhinitis as risk factor for Bronchial asthma
If with allergic rhinitis, 3-fold increased risk for developingbronchial asthma
If with allergic rhinitis and sinusitis, 6-fold risk for developingBronchial asthma
o 80% of Bronchial asthma patients have Allergicrhinitis
o 40% of allergic rhinitis patients will haveBronchial asthma
Diagnostic tests
All positive results have to be correlated with clinicalsensitivity
Skin testing
Primary diagnostic tool In vivo diagnostic evaluation that can help confirm allergen-
specific antibodies
o Immediate hypersensitivity reaction Simple, easy to perform, low cost, high sensitivity Uses
o To diagnose IgE-mediated allergyo Epidemiology studieso Standardization of allergen extractso
Pharmacologic studieso Avoidance strategieso Immunotherapyo Desensitization
Beneficial with:o Inhalant allergenso Insect venomo Food allergieso Drugs
Only Penicillin is validatedo Latex
Important to strongly weigh potential risk for patients whoare:
o Pregnanto Taking in medications
Beta Blockers Common indoor allergens that tested positive (UP-PGH
Clinic, 1998 by Pring A and Recto M)
Allergens Percent
House dust 74
cockroach 44.7
Mosquito 15.7
Dogs hair 13.5
Cats hair 1.9
Mixed Molds 8.1
Kapok (organic cotton) 5.9
Mixed feathers 1.6
Common Outdoor Allergens that tested positive (UP-PGHClinic, 1998 by Pring A and Recto M)
Allergens Percent
Bermuda Grass 14.1
Korokorosan 9.7
Ipil-ipil 9.2
Corn pollen 8.6
Egyptian grass 6.5
Pigweed 6.5Yard grass 6.45
Mutha 6
Cogon 5.5
Makahiya 4.9
Amorseco 4.9
Rice pollen 4.4
Precautionso Systemic reactions to Allergic skin testing
33/100, 000 tests (Mayo Clinic) Varies according to the material
tested
Aeroallergens: 23/100,000o 0.02%
Antibiotics: 72/100, 000
o 0.07% Latex: 228/100, 000
o 0.23% Varies according to method
Prick test: 30/100, 000 Intradermal test: 55/100,
000
Fatal reactions Immunotherapy:
o 1:2.5 Mo 3-4 deaths per
year
o Antihistamines must be discontinued prior to skintesting
1stgeneration: up to 24 hours 2ndgeneration: 3-10 days (7 days) Astemizole: 60 days Topical H1 antagonist: 2 weeks Ketotifen: >5 days
o Antidepressants: 3 weekso Leukotrienes: 2 dayso Steroids
No effect on Skin test unless high dose Potent topical: 14-21 days
o Theophylline: slight reductiono Beta blockers: increases skin test reactivity
Modified Prick test
Most specific test available but less sensitive thanintradermal testing
Identifies most clinically significant allergens
Only 2 areas allowedo Volar aspect of forearm
5cms from the wrist to 2-3 cms fromthe antecubital fossa
o Back Only method that should be used for food allergens Measure the wheal or flare
o (+): 3mm or more
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Intradermal tests
More sensitive than epicutaneous but less specific Increased risk of systemic reactions Done when the Modified Prick test is negative
In vitro tests (RAST testing)
Designed to screen for the presence of allergen-specific IgEin the patients serum byusing immobilized allergen on a
solid phase
May give false positive resultso Because they only rely on IgE in the blood and
not mast cell degranulation
Sensitivity Specificity
Unicap 78-94% 77-94%
PPV NPV
Aeroallegen Skin Test 95% (97-99%) >95%
Food Allergen Skin Test 95%
Physical Examination
Key components
Appearanceo Allergic facies
Allergic shiners Allergic salute Mouth breathing Dennie Morgan Nasal crease
o Rashes Macular Papular Lichenification Urticaria Angioedema
Skin examo Urticariao Angioedemao Dermographismo Atopic dermatitiso Others
Maculopapular Blisters
Wheals/hives Erythema multiforme SJS TEN
o *percentage of SJS and TEN???o Skin lesions in atopic dermatitis
Note the appearance and distribution
HEENTo Eyeso Earso Nose
Swollen and edematous turbinates
Polyps Septal deviation Ulceration Perforation
Pulmonary
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o Thorough lung exam is required Check for wheezing or an increased
expiratory phase
Forced expiratory maneuver may behelpful
o PEFR M: ht in cms100 x 5 +175 F: ht in cms100 x 5 + 170
Management
Principles
Treatment must be individualized Avoidance of allergens and irritants Judicious use of pharmacologic agents Administration of immunotherapy Patient education
Environmental allergen and irritant avoidance
First step in the management of allergic disease Always a part of patient education Phenomenon of polysensitization Avoidance or limitation of pro-allergic lifestyles
o Pro-allergic lifestyles include: Increased urbanization Sedentary lifestyles Greater time spent indoors Climate change Stress Infections Obesity/Diet
Allergenso House dust miteo Pollens
Trees Grasses Weeds
o Moldso Animal dandero Cockroach
Irritantso Cigarette smokeo Strong odorso Air pollution,
Sulphur NO2 Diesel fumes
o Sudden changes in temperaturePharmacotherapy
Antihistamineso Mainstay of therapyo Older generation
Sedating Use should be individualized
Ethanolamine Clemastine
Diphenhydramine
Ethylenediamines Tripelenamine
Antazoline
Alkylamines Chlorpheniramine
Brompheniramine
Dimethindine
Phenothiazines Promethazine
Methdilazine
Piperazines Hydroxyzine
Meclizine
Buclizine
Piperidines Cyproheptadine
Azatidine
o Newer generation Acrivastine Cetirizine Azelastine Ebastine Loratadine Levocitirizine Fexofenadine Desloratadine Non-sedating and with longer
duration of action
Decongestants Anti-leukotrienes Nasal chromones Bronchodilators Inhalational corticosteroids Newer therapeutic modalities
o Immunomodulators Vit C
o Anti-IgE Omalizumab
o Cytokine antagonistsAllergen immunotherapy
Administration of increasing quantities of specific allergicextracts
o To alter the immunologic response of patientso With IgE-mediated Allergic rhinitis, asthma or
insect sting anaphylaxis
Should always be given by an Allergology specialisto Proper instructions for emergency management,
like anaphylaxis
Immunotherapy: Sites of Actions
IgG
IL2, IFN-y IgE
IL4, IL5
IL4, IL5
Patient education
Dont wear woolo The sharp fibers irritate skino Watch for other places you might come into
contact with wool besides your own clothing
Avoid clothes made from other itchy or stiff fabrics such as:o Polyestero Nylono Acrylic
Wear soft, loose-fitting cotton clothes Remove clothing tags that rub against the skin Avoid clothes with rough seams or trim
Modified Allergen
Extract s.c.
Mast Cell
Allergic Inflammation
MHC ClassII TCR
TH Cell Precursor
Activated TH2 Cell
Activated TH1
Cell
IgG producing B Cell
IgE producing B cell
Block
modif
Acute P
Reacti
Blocked by ITInduced by
IT
Blocked by
IT
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Avoid playing on grassy areas and forested areas especiallyduring pollen seasons
When cleaning, make use of a water or oil mop instead ofbrooms
Key Points
A well organized and thorough history is critical indiagnosing allergic diseases
Diagnostic evaluation with skin testing or RAST testing todetermine allergic sensitization must always be correlated
with clinical symptoms
The physical examination should be directed towards themajor target organs of allergic diseases
Managemento 4pronged approach
Patient education Allergen avoidance Medications Immunotherapy
Adverse Drug Reactions
Epidemiology Estimates of up to 15% of drug administrations culminate in
an Adverse drug reaction
o The risk is doubled in the hospital settingo Fatal drug reactions occur in approximately 0.1%
of medical inpatients and 0.01% of surgical
inpatients
Immunologic drug reactions or allergic drug reactionsaccount for only 5-10% of all adverse drug reactions
Classification
Type A (Augmented)o Predictableo Usually dose dependento Excessive pharmacologic or therapeutic action or
as a manifestation of the drugs pharmacologic
effect but occurring at some other site
Type B (Bizarre)o Unpredictableo Bizarre effectso Unrelated to the known pharmacologic
properties of the drug
o Caused by: Genetic Immunologic Neoplastic Teratogenic
Predictableo Dose dependento Related to the known pharmacologic actions of
the drug
o Occur in otherwise normal patientso 80% of Adverse drug effectso Overdosage
Toxicityo Side effects
Immediate expression Delayed expression
o Secondary or indirect effects Drug related Disease-associated
o Drug to drug interactions Unpredictable
o Usually dose independento Usually unrelated to the known pharmacologic
action of the drug
o Often related to the individuals immunologicresponsiveness or on occasion, to genetic
differences in susceptible patients
o Intolerance Characteristic pharmacologic effect of
a drug
Quantitatively increased Produced by an unusually small dose
of medication
Eg. Tinnitus after Salicylates andQuinine even in small doses in a few
number of patients
o Idiosyncratic reactions A qualitatively abnormal, unexpected
response to a drug, differing from its
pharmacologic actions and thus
resembling hypersensitivity
Eg. Hemolytic Anemia in African andMediterranean population and in 10-
13% of African American males
exposed to oxidant drugs or their
metabolites
o Allergic (Hypersensitivity) reactions Result of an immune response to a
drug following previous exposure to
the same drug or to animmunochemically related substance
that had resulted to the formation of:
Specific antibodies Sensitized T lymphocytes Both
Eg. Anaphylaxis secondary to anadverse drug reaction to Penicillin
Type Mechanism Example
Type I IgE antibodies
leading to mast
cell/basophil
degranulation
Penicillin -
anaphylaxis
Type II IgG/IgM-mediated
Cytotoxic reaction
against cell surface
Quinidine
Hemolytic anemia
Type III Immune complex
deposition reaction
Cephalexin - serum
sickness
Type IV T lymphocyte
mediated reactions
(CD4 and TH1) type 1
cytokines
NeomycinContact
dermatitis
o Pseudoallergic reactions Immediate generalized reaction
involving mast cell mediator release
by an immunoglobulin (IgE)-
independent mechanism
Eg. Opiates Vancomycin
o RedmansSyndrome
D-tubocurarine Adverse drug reactions Adverse drug experience/events
o In conjunction with the treatmentRisk Factors for Drug Allergy
Patient related factorso Age and gender
Younger and Older: immature immunesystem
o Genetic factorso Prior drug reactions
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o Concurrent medical illness Cancer
o Concurrent medical therapy Drug and Treatment related factors
o Nature of the drug Immunologic reactivity Non-immunologic reactivity
o Drug exposure Route of administration Dose, duration, frequency of
treatment
Approach to Management of ADRs
Detailed history
Thorough history taking and information gatheringo What were the signs and symptoms? In what
order did they appear and resolve?
o What was the time course of the putativereaction?
o Why was the drug prescribed? Can any sign orsymptom be explained by intercurrent illness?
o What other drugs was the patient taking at thetime of putative reaction?
o Has the patient ever received the drug, or drugsin the same or related class before? If so, how long ago, and what was the
outcome?
Drug Charto An integral part of the history
Aug7 Sept13 Oct8 Oct12
Multivitamins (Cherifer)
Amoxicillin (Amoxil)
Paracetamol (Naprex)
Oxacillin (Pharex)
Pruritic maculopapular
rash on trunk and face,
progressive
Clearing
o List all the number of drugs being taken includingbrands (even lot numbers)
o Accurately plot schedule of intakeo Query and list all symptoms, distribution and
course of rashes
Morphology Mechanism unknown (presumed immunologic)
o Stevens-Johnson syndrome 10-30%
o Toxic epidermal necrolysiso Drug fever
Considered a Drug fever if upondiscontinuation of the drug, the feverlysed within 3 days
Discontinue drugfever lysed within3 days
o Acute interstitial nephritiso Pulmonary infiltrates with eosinophilia
Factors influencing immunologic drug reactionso Route of administration
Parenteral route is more immunologicthan oral route
o Dosing Higher doses > lower doses
o Time interval Shorter intervals > longer intervals
o Timing of doses
Multiple, intermittent doses > singledose
o Drug structure High molecular weight > Low
molecular weight
o Host characteristicsPositive Influence No Influence
Age (Adults > Children and very
old)
Family history of atopy
Gender (Females > Males) Atopy (Beta lactams)
Presence of infection or
concurrent medical illness
History of reaction to any drug
Personal or family history of
multiple drug allergies
Atopy (in some cases of NSAIDs,
RCM)
Skin test
reagents
Route Drug test
concentration
Skin test
volume
Dose
Penicilloyl-
polylysine
(pre-Pen) (6 x
10-5 M)
Prick
Intradermal
Full strength
Full strength
1 drop
0.02 ml
Penicillin G
Potassium
(Freshly
prepared)
Prick
Intradermal
(Serial 10-
fold
dilutions
optional)
10, 000 u/ml
10, 000 u/ml
1 drop
0.02 ml
200 units
Penicillin
minor
determinant
mixture (10-2
M)
Prick
Intradermal
(Serial 10-
fold
dilutions
optional)
Full strength
Full strength
1 drop
0.01-0.2
ml
Cephalosporins
and other
Penicillins
Prick
Intradermal
(Serial 10-
folddilutions
optional)
3 mg/ml
3 mg/ml
1 drop
0.02 ml
60 ug
Aztreonam Prick
Intradermal
(Serial 10-
fold
dilutions
optional)
3 mg/ml
3 mg/ml
1 drop
0.02 ml
60 ug
Imipenem Prick
Intradermal
(Serial 10-
fold
dilutions
optional)
1 mg/ml
1 mg/ml
1 drop
0.02 ml
20 ug
Histamine-
positive
control
Prick
Intradermal
1 mg/ml
0.1 mg/ml
1 drop
0.02 ml
Saline or
diluents-
negative
control
Prick
Intradermal
NA
NA
1 drop
0.02 ml
Supportive treatment Educate patient
Diagnostic Tests
In vivo testing
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Dr. T. Tolentino
1
~clarissalee
o Clinically indicated in some caseso Cutaneous tests for IgE-mediated reactionso Patch testso Incremental provocative testing
In vitro testingo Rarely helpful clinicallyo Drug-specific IgE antibodies (RAST)o Drug-specific IgG and IgM antibodieso Others
IC detection Complement activation Mediator release
Withdrawal of the suspected drugo Presumptive evidence if the symptoms clear
(-) (+) (+) (-)
(-) (+) (-)
Treatment Options
Desensitizationo
Should be considered in patients who have anIgE-mediated allergy to medication and no
acceptable alternate treatment is available
o Aim To convert a patient who is highly
allergic to a drug to a state where they
can tolerate treatment with the
medication
Mast cells are renderedunresponsive to the drug
Graded Challengeo Test dosing
Cautious administration of amedication to a patient who is unlikely
to be truly allergic to it
Generally, the starting dose is 1/10 to1/100 of the full dose and
approximately 5-fold increasing doses
are administered every 30 minutes
until the full therapeutic dose is
reached
Discontinueo Or substitute with a non-cross reacting agento All drugs that have both a temporal relationship
to the putative allergic reaction and known
allergic potential
Consider skin testing if available and reliable Consider Provocative dose challenge or Desensitization if
one of the suspected drugs is again clinically indicated
Corticosteroids Manage anaphylaxis
o EpinephrinePrevention
Administer an alternate Administer a potentially non-cross reactive drug under close
medical supervision
Provocative dose challenge Pre-treatment protocols Perform Desensitization
o If no acceptable alternative drug exists
Urticaria
Circumscribed raised areas of erythema and edemainvolving the superficial portions of the dermis
Usually multiple and pruritic Acute urticaria
o Less than 6 weeks Chronic urticaria
o More than 6 weeksDiagnostics
Acute Urticariao CBCo Urinalysiso Stool examo Chest X-ray, PPD (Purified Protein Derivative)
Chronic Urticariao CBCo Chest X-rayo FBS, BUN Creatinine, Liver Function Testso FT4, TSHo H. Pylori tests
Management
Insect Allergy
Stinging or biting
History of Penicillin Allergy
Skin Test with Pre-
Pen, Pen G, and
MDM
Give Pen 1. Give alternate antibiotic
2. Desensitize to Penicillin
Skin test with Pre-Pen
and Pen G only (MDM
not available)
1. Give Penicillin via
Graded Challenge
2. Desensitize if reaction
severe and recurrent
History of Amoxicillin Allergy
Skin Test with Pre-Pen,
Pen G, and MDM, and
Amoxicillin
Give
Amoxicillin
1. Give alternate antibiotic
2. Desensitize to Amoxicillin
Skin test with Pre-Pen
and Pen G only (eitherMDM or Amoxicillin not
available)
1. Give Amoxicillin via
Graded Challenge
2. Desensitize if reaction
severe and recurrent
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8/13/2019 Pediatric Allergology_Dr. T. Tolentino (2)
13/14
Dec. 13, 2013, Jan. 6, 2014
Dr. T. Tolentino
1
~clarissalee
o Localized cutaneous reactions to anaphylaxis Inhalation of airborne particles of insect origin
o Acute and chronic respiratory symptoms ofrhinitis, conjunctivitis or asthma
Incidence
0.4-0.8% of children 3% in adults 40 deaths/year in the US
Etiology
Mostly localizedo Biting or stinging mosquitoeso Flieso Fleas
Occasionally, pronounced localized or systemic reactions:Type 1 or delayed
o IgE-mediatedo Hymenoptera order
Apids Honeybee Bumblebee
Vespids Yellow jacket Wasp Hornet
Formicids Harvester ants Fire ants
Systemic manifestationso Seasonal or perennial symptoms of the upper
and lower airways
Seasonal Caddis fly and the midge
o When larvaepupate and
adult flies are
airborne
Perennialo Cockroach
sensitizationo House dust mite
Pathogenesis
Localized reactionso Vasoactive or irritant materials from the insect
saliva
o Hymenoptera venoms Toxic and pharmacologic activity and
with allergy potential
Vasoactive substances Histamines Acetylcholine Kinins
Enzymes Phospholipase Hyaluronidase
Appamin Mellitin Formic acid
Cross reactivity among vespids is substantial Systemic responses: IgE mediated
o Caddis fly Hemocyanin-like protein
o Midge fly Haemoglobin-derived allergen
o Cockroach Proteases Troponin Tropomyosin
Lipocalin from saliva, secretions, fecalmaterial and debris from skin casts
Clinical Manifestations
Localizedo Less than 24 hourso Self limiting
Large local reactionso >10 cmso Lasts for days
Generalized cutaneous reactionso Rapidly progressingo Cutaneouso Urticariao Angioedema beyond the sting site
Systemic reactionso Anaphylaxiso Toxic reactionso Delayed/late reactions
Serum sickness Vasculitis Nephrotic syndrome Neuritis Encephalopathy
Inhalational allergy from insectso Depends on individual exposureo Rhinitiso Conjunctivitiso Asthma
Mosquito biteo Depends on the CO2 content of skino Papaya leaf: no necrolysis
Diagnosis
History of exposure Typical symptoms Physical examination Venom specific IgE by skin testing
o For venom immunotherapyo Clinical confirmation
Prevention and treatment
Avoidance is essentialo Avoid attractantso Proper clothing and protectiono Nest removal
Supportive for localized stings Anaphylaxis management Venom immunotherapy Inhalant allergy management
Ocular Allergies
Common target of allergic disorders because of its markedvascularity
Conjunctivao Most immunologically active tissue of the
external eye
Occurs as localized or together with allergic rhinitisClinical manifestations
All with bilateral involvement Sensitization is necessary for all except for giant papillary
conjunctivitis
Incidence Etiology Involvement
Allergic
conjunctivitis
Most
common
Direct exposure
to
Variable ocular itching
more than pain
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8/13/2019 Pediatric Allergology_Dr. T. Tolentino (2)
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Dec. 13, 2013, Jan. 6, 2014
Dr. T. Tolentino
1
30% of
population
environmental
allergens
Increased tearing
Bilateral injected
conjunctivae
Chemosis
Watery discharge
Vernal
kerato-
conjunctivitis
In patients
with
seasonal and
perennial
allergies
Those with
AD
Exposure to
irritants, light,
perspiration
Limbal or palpebral
form:
Severe itching
Photophobia
Foreign body
sensation
Stringy or ropey
discharge
Trantas dots
Corneal ulcers
Cobblestoning
Dennie Morgan folds
Longer eyelashes
Gant Papillary
Conjunctivitis
Chronic
exposure to
foreign bodies:
contact, lenses,
ocular
prostheses,
sutures
Mild ocular itching,
tearing, excessive
ocular discomfort,
mucoid discharge,
with white or clear
exudates on
awakeningthick and
stringy, Trantas dots,edema, hyperemia
Atopic
Kerato-
conjunctivitis
Rarely before
late
adolescence
Almost all with
Atopic
Dermatitis
Severe itching,
burning, tearing all
year round, injected
and chemotic bulbar
conjunctiva and skin
involvement
Contact
Allergy
Exposure to
topical
medications,
contact lens
solution,
preservatives
Eyelids and
conjunctivae
Treatment
Primaryo Avoidance of allergenso Cold compresseso Lubrication
Secondaryo Use of topical or systemic antihistamineso Topical decongestantso Mast cell stabilizerso Anti-inflammatory agents
Tertiaryo Topical or oral corticosteroids
Referred to Ophthalmologisto Allergen immunotherapy
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