pediatric allergology_dr. t. tolentino (2)

8/13/2019 Pediatric Allergology_Dr. T. Tolentino (2)

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Dec. 13, 2013, Jan. 6, 2014

Dr. T. Tolentino

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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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Dr. T. Tolentino

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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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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


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


14/14

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

pediatric allergology_dr. t. tolentino (2)

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