dr lani allergi for Pharmacy classpdf.pdf

Imunologi

1. Lani Hamijoyo
Allergy
Laniyati Hamijoyo
Rheumatology Division
Departement of Interal medicine
Universitas Padjadjaran/ Hasan Sadikin Hospital
Bandung Indonesia

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§ Type of hypersensi2vity reac2ons of the immune system. Allergy may
involve more the one type of reac2on.
§ An allergy is a immune reac2on to something that does not affect most
other people. Substances that o?en cause reac2ons are:
q Pollen
q Dust mites
q Mold spores
q Pet dander
q Food
q Insect s2ngs
q Medicines
q …….
Allergy

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Risk factor
§ Host factors; heredity, gender, race, and age.

§  Environmental factor; infectious diseases during early
childhood, environmental pollution, allergen levels
and dietary changes.

Allergy

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Figure 10-1

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§ Hypersensitivity (hypersensitivity reaction)
refers to undesirable immune reactions
produced by the normal immune system.

§ Hypersensitivity reactions require a pre-
sensitized (immune) state of the host.


Hypersensi-vity

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• 4 main hypersensi2vi2es (I-IV)
– Type I Anaphalaxis; Immediate; IgE mediated mast
cell degranula2on
• Allergies, atopy
– Type II Cytotoxic (IgM and IgG mediated)
• autoimmune hemoly2c anemia, pemphigus vulgaris
– Type III Immune complex
• Serum sickness, RA, SLE
– Type IV DTH/contact sensi2vity
• Contact derma22s
Hypersensitivity reactions

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Type of Hypersensi2vity

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Hypersensi-vity Reac-ons
!

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Allergy
Ig E mediated (Type I
hypersensitivity)
Non Ig E mediated
Allergy

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§ Overreaction to an allergen that is contact through skin,
inhaled through lung, swallowed or injected.

§ Triggered by harmless substances such as; pollen, dust,
animal danders, food, … can also occur as a result of
drug or bee stings or stings from other insects (an
allergen).

§  An allergen; an antigen that causes allergy. Either
inhaled, ingested, .. Can be complete protein antigens
(Pollen and animal dander) or low molecular weight
proteins.
IgE Mediated: Type I

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§ Atopy is the genetic predisposition to make IgE antibodies
in response to allergen exposure.

§ Etiology is unknown but there is strong evidence for a
complex of genes with a variable degree of expression
encoding protein factors.

§ Allergic rhinitis, allergic athma, atopic dermatitis are the
most common manifestation of atopy. These manifestation
may coexist in the same patients at different times. Atopy
can be asymptomatic.

Atopy

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§ Proteins
q Foreign serum
q Vaccines
§ Plant pollens
q Rye grass
q Ragweed
q Timothy grass
q Birch trees
§ Drugs
q Penicillin
q Sulfonamides
q Local anethe2cs
q Salicylates
§ Foods
q Nuts
q Seafood
q Eggs
q Peas, beans
q Milk
§ Insect products
q Bee venom
q Wasp venom
q Ant venom
q Cockroach calyx
q Dust mites
§ Mold spores
q Animal hair and dander
Common allergens associated with type I hypersens2vity

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Immuno
pathogenesis

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§ Mast cell are abundant in the mucosa of the
respiratory, gastrointestinal tracts and in the skin,
where atopic reaction localize.
§ Mast cell release mediator cause the pathophysiology
of the immediate and late phases of atopic diseases.
Mast Cell

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Mast Cell Ac-va-on

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Histamine:
This mediator acts on histamine 1(H1) and histamine 2 (H2) receptors to
cause:
- contraction of smooth muscles of the airway and GI tract,
- increased vascular permeability and vasodilation,
- nasal mucus production, airway mucus production,
- pruritus,
- cutaneous vasodilation, and gastric acid secretion.


Serotonin: increased vascular permeability and contraction of smooth
Muscles.

Performed Mediators/ Primary Mediators

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Performed Mediators/ Secondary Mediators


– Platelet activating factor
– Leukotriens
– Prostaglandinin
– Bardykainin
– Cytokines
– IL1 ,TNF
– IL2,IL3,IL4,IL5,L6

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Important Clinical Aspects of Immediate
Hypersensitivity
Main organ Disease Main symptoms Typical allergens Route of entery
Lung Asthma Wheezing,
dyspnea,
tachypnea
Pollens, house
dust, animal
danders
Inhala2on
Nose and Eyes Rhini2s, conjunc2vi2s
Hay fever
Runny nose,
redness and
itching of eyes
Pollens Contact with
mucous
membrane
Skin Eczema (atopic
derma22s)
Ur2caria
Pruri2c,
vesicular lesions
Pruri2c, bullous
lesions
Uncertain
Various foods
Drugs
Uncertain
Inges2on
Various
Intes2nal tract Allergic
gastroenteropathy
Vomi2ng
diarrhea
Various food Inges2on
Systemic Anaphylaxis Shock,
hypotension,
wheezing
Insect venom;bee
Drugs; penicillin
Foods; Peanuts
S2ng
Various
Inges2on

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§ Hypersensitivity pneumonitis involves inhalation of
an antigen. This leads to an
exaggerated immune response
(hypersensitivity). Type III hypersensitivity and type
IV hypersensitivity occur in hypersensitivity
pneumonitis.


§ 
Allergic contact dermatitis.
§ 
…

Allergic Hypersensi-vity: Non IgE Mediated

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"

Result

Antigen source Mechanism Disease
Disease

Foreign Immunologic Allergy
Prophylaxis

Foreign Immunologic Immunity
Disease

Self Immunologic Autoimmunity
Disease

Foreign Toxic Toxicity
Comparison of Allergy with other Responses

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Laboratory Diagnosis

Skin Tests
Blood Tests
IgE-Mediated
Allergies

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§ The cutaneous test
§ (prick test, puncture test epicutaneous test)
§  Routine diagnosis in diseases (atopic or anaphylactic).
§ A single drop of concentrated aqueous allergen extract
placed on the skin which is then pricked lightly with a
needle point at the center of the drop. After 20 minutes the
reaction is graded and recorded
Skin Tests

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§ IgE levels may be elevated in patients who are atopic,
but the level does not necessarily correlate with
clinical symptoms.
§ The tryptase level can be elevated, which is indicative
of mast cell degranulation. False-negative results can
occur.
§ An elevated eosinophil count may be observed in
patients with atopic disease.
§ RAST/CAP RAST/CAP FEIA (fluorenzymeimmunoassay):
measures antigen-specific IgE.
Laboratory Tests

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§ Nasal smear
§ Elevated eosinophil levels can be consistent with
allergic rhinitis.
§ Spirometry or pulmonary function tests
§ offer an objective means of assessingasthma. Peak-
flow meters can also be used for this and can be
used by patients at home to monitor their status
Nasal smear/ Spirometry

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Standardized diagnostic allergens are not available for drugs

Penicillin is the only drug for which a standardized diagnos2c
allergen exists. While nonstandardized skin tests can be
performed for the minor determinants in penicillin or for other
drugs (ie, by pricking the skin where drug solu2on has been
placed), these tests are only useful if findings are posi2ve.

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Prevention
§ Avoid triggers such as foods and medications,…… that
have caused an allergic reaction, even a mild one. This
includes detailed questioning about ingredients when eating
away from home. Ingredient labels should also be carefully
examined.
§ A medical ID tag should be worn by people who know that
they have serious allergic reaction.
§ If any history of a serious allergic reactions, carry
emergency medications (such as diphenihydramine and
injectable epinephrine.
§ Do not use your injectable epinephrine on anyone else. They
may have a condition (such as a heart problem) that could
be affected by this drug.

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Treatment

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Allergic Reactions
Anaphylaxis (Greek = "backward protec-on")
Rapid generalized immunologic reac-on aKer exposure to
an-gens in a sensi-zed person, with at least 2 of :

a. respiratory/ airway compromise from swelling or wheezing
b. hypotension or cardiovascular collapse
c. diffuse cutaneous findings (ur-caria, angioedema, +/-
erythroderma)

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Allergic Reactions
Anaphylactoid reac-on :
Syndrome presen-ng similar to anaphylaxis, expressed by similar
mediators, but not triggered by IgE & not necessarily due to prior
exposure to the inci-ng agent
Ur-caria :
Diffuse patchy erythematous pruri-c rash with raised borders
Angioedema :
Non-piWng subcutaneous -ssue swelling
OKen of the face, mouth, or peri-airway -ssue

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Case: Angioedema Due to ACE Inhibitors
• Occurs in 0.2 % of pa-ent on ACE inhibitors
• Can occur even aKer prolonged use of ACE inhibitors
without a prior reac-on
• Predilec-on for head & neck angioedema so airway
compromise possible
• Rx by stopping the ACE inhibitor, epi, steroids,
diphenhydramine, +/- airway management

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Severe angioedema

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Same patient on prior
slide after treatment

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Clinical Manifestations of Systemic
Allergic Reactions
• Diffuse pruri-s, ur-caria, angioedema, erythroderma
• Anxiety, dizziness, sense of doom, altered mental status
• Dyspnea, stridor, wheezing
• Dysphagia, dysarthria, drooling
• Vomi-ng, diarrhea, abd. cramps
• Urinary incon-nence
• Hypotension +/- bradycardia

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Differential Dx of Severe Allergic Reaction
Sudden loss of consciousness :
vasovagal syncope, seizures, dysrhythmias, CVA
Acute respiratory distress :
status asthmatics, upper airway infection, foreign
body aspiration, pulmonary embolus
Cardiovascular collapse :
intraabdominal bleed, acute MI
Systemic disorders :
mastocytosis, hereditary angioedema (C1 esterase deficiency
syndrome) , carcinoid syndrome,, MSG syndrome

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Management of Systemic Allergic Reactions
• May progress rapidly & unpredictably, all patients. with
possible systemic reaction should be rapidly triaged to
acute care room & continuously monitored
• Suggested initial sequence :
• O2 / airway management
• SQ or IM epi (0.01 mg/kg or max. 0.3 mg in adults)
• IV placement ; IV fluid bolus (NS) if hypotensive
• IV diphenhydramine & IV steroids
• Beta 2 aerosol if wheezing
• Secondary meds ; consider repeat epi doses
• Remove source of reaction if possible

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Airway Management Considerations for
Severe Allergic Reactions
• Swelling impinging the airway may progress rapidly so
earlier intuba-on more likely successful than later
• Consider seda-on without paralysis if an-cipated difficulty
• Start with ETT size one size smaller than usual
• Have surgical airway equipment at bedside
• Place nasal airway early even if ETT not ini-ally required
• Consider use of inhaled racemic epi

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Potential Complications of Use of Epi for
Allergic Reactions
• Hypertension (may cause CNS bleed)
• Increased myocardial O2 consumption
• Coronary vasoconstriction
• Tachycardia / dysrhythmias

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Epi Doses for Allergic Reactions
• Give IM or SQ if unable to start IV line quickly
• Give IV if markedly hypotensive
• IM or SQ dose : 0.01 mg/kg
• 0.01 ml/kg of 1:1000 ; max. dose 0.3 mg
• IV dose : 0.1 mg (max.)
• 1 cc of 1:10,000
• Repeat as needed
• Can also give via MDI (10 to 20 puffs)

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Antihistamine Med Rx for Allergic Reactions
• Act by competitively inhibiting H1 & H2 receptors
• Diphenhydramine is best single agent against pruritis,
but combo Rx (with H2 blocker) is superior
• Give PO for mild & local reactions
• Give IM only if airway compromise & unable to start IV
• Give IV for severe reactions
• Usually give 50 mg diphenhydramine, & 300 mg
cimetidine or 50 mg ranitidine

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Steroid Rx for Allergic Reactions
• Have an--inflammatory effects, stabilize mast cell
membranes, & may blunt the biphasic response
• Indicated in almost all pts. with systemic reac-ons
• Usually 100 mg hydrocor-sone or equivalent is sufficient
• May need 1 to 2 days follow-on oral use (prednisone 40 mg/
day) depending on source of reac-on
• Give PO if airway & BP not compromised, otherwise give IV

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Summary
• 4 types of Hypersensi2vity reaac2on
• Allergy is IgE mediated and non IgE mediated
• Treatment : Avoid Allergen, Allergy therapy
• Educa2on

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