ANAPHYLAXIS

HYPERSENSITIVITY REACTIONS WITH AN OVERVIEW ON ANAPHYLAXIS

VARSHIL MEHTAINT. ROTATING M4 STUDENT

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OBJECTIVESBRIEF INTRODUCTION ON HYPERSENSIVITYDEFINITIONCLASSIFICATIONOVERVIEW ON ALL TYPESANAPHYLAXIS

BACKGROUNDIt was coined by Von Pirquet in 1906.

Hypersensitivity reactions over reaction of the immune system to harmless environmental antigens or agents like pollens.

It occurs when an already sensitized individual is re-exposed to the same foreign substance.

Terms hypersensitivity and allergy are used interchangeably

DEFINITIONHYPERSENSITIVITY REACTION

A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign agent.

These reactions may be damaging, uncomfortable, or occasionally fatal.

Coombs and Gell classified hypersensitivity into 4 types.

Coombs and Gells Classification

TYPE 1 HYPERSENSITIVITY

Commonly called as allergy and can occur within minutes

Mediated by IgE antibodies in response to stimulation of Th2 cells by an antigen.

The antigens that stimulate it are called allergens (i.e. House dust, Pollens, Cosmetics, Insects, Clothing and Drug)

Exposure may be ingested, inhalation, injection or direct contact.

Type I hypersensitivity reactions can be systemic (e.g., systemic anaphylaxis) or localized to a specific target tissue or organ (e.g., allergic rhinitis, asthma, Allergic conjunctivitis, urticarial,eczema).

TYPE II: CYTOTOXIC REACTIONS Body makes special IgG autoantibodies directed against self cells that have some form of foreign protein attached . Hence IgG mediated Antigen: 1. may be intrinsic to the cell membrane 2. may take the form of an exogenous antigen adsorbed on the cell surface.Hypersensitivity results from the binding of antibodies to normal or altered cell-surface antigenClinical examples include hemolytic anemias, thrombocytopenic purpura, hemolytic transfusion reactions, Goodpastures syn drome, and drug-induced hemolytic anemia

TYPE III: IMMUNE COMPLEX REACTIONSExcess antigens cause immune complexes to form in blood; these circulating complexes usually lodge in small blood vessels Usual sites include kidneys, skin, joints & small blood vesselsLodge in the small vessel walls, trigger inflammation & cause tissue or vessel damageExamples: rheumatoid arthritis, systemic lupus erythematosus & serum sickness

TYPE IV: DELAYED HYPERSENSITIVITY REACTIONSReactive cell T-lymphocyte (T-cell)Antibodies & complement not involvedLocal collection of lymphocytes & macrophages causes edema, induration, ischemia & tissue damage at site within hours to days after exposureExamples: Tb test (positive purified protein derivative), contact dermatitis, poison ivy skin rashes, insect stings, tissue transplant rejection & sarcoidosis

ANAPHYLAXIS

WHAT IS ANAPHYLAXISAna (without), phylaxis (protection).

Acute multi-systemic allergic reaction involving the skin, airway, vascular system, and GI.

Anaphylaxis is defined as a serious allergic or hypersensitivity reaction (type 1) that is rapid in onset and may cause death.

HISTORY SPEAKS

1st recorded 2640 BC in hieroglyphicsThe story of sudden death of a pharaoh after a bee stingRichet & Portier coined term anaphylaxis to describe the unexpected effect during immunization of the dogs.

The prevalence of anaphylaxis in the general population is at least 1.6% and probably higher - Robert A. Wood, journal of allergy and clinical immunology, 2013.

The incidence rate is from 1.21% to 15. 5 % in general population. Neugut, 2001-Arch Int Med

Mortality rate -2.4 per million in US. INCEDENCE AND PREVALANCE

ETIOLOGY

U.S. TOP 8FishCrustacean ShellfishEggMilkPeanutsTree-nutsSoyWheatGluten ?

SesameMolluscsSulfites GlutenCanadaTop 8 Plus

+ Sesame+ Molluscs+ Sulfites+ Gluten + Celery+ Mustard+ LupinE.U.Top 8 PlusBuckwheat

Another 20 allergens are recommended

Japan4 of Top 8*Milk*Egg*Peanuts*WheatPlus+ Buckwheat

SesameMolluscsSulfitesGlutenAustralia/NZ Top 8 Plus

+ Gluten (in place of wheat)+ Sulfites

CodexTop 7 Plus

SulfitesGluten (in place of wheat)Hong Kong Top 7 Plus

International Food Allergen ListINTERNATIONAL FOOD ALLERGEN LIST

ETIOLOGY

PATHOPHYSIOLOGYFirst exposureActivation of TH2 cell Stimulate IgE switiching

Allergen

TH2 Cell

B Cell

PathophysiologyFirst exposureIgE productionIgE secreting B cell

IgE

PATHOPHYSIOLOGYFirst exposureIgE bind to mast cell

Mast cellFcRIIgE

PATHOPHYSIOLOGYSecond exposureRecognition

AllergenMast cellFcRIIgE

PATHOPHYSIOLOGYSecond exposureActivation of mast cell to release histamine and other mediators

AllergenMediatorsMast cellFcRIIgE

PATHOPHYSIOLOGY

SIGNS & SYMPTOMS

Skin

SIGNS & SYMPTOMSEyes

SIGNS & SYMPTOMSNose & mouth

SIGNS & SYMPTOMSLungs and throat

SIGNS & SYMPTOMSHeart and circulation

SIGNS & SYMPTOMSDigestive system

SIGNS & SYMPTOMSNervous system

DIFFERENTIAL DIAGNOSISPRESENTATIONDIFFERENTIAL DIAGNOSISHypotensionSeptic shockVasovagal reactionCardiogenic shockHypovolemic shockRespiratory distress with wheezing or stridorAirway foreign bodyAsthma and chronic obstructive pulmonary disease exacerbationVocal chord dysfunction syndromePostprandial collapseAirway foreign bodyMonosodium glutamate ingestionSulfite ingestionScombroid fish poisoningFlush syndromeCarcinoidPostmenopausal hot flushesRed man syndrome (vancomycin [Vancocin])MiscellaneousPanic attacksSystemic mastocytosisHereditary angioedemaLeukemia with excess histamine production

An increased amount of tryptase protein can be measured in a blood sample collected during the first three hours after anaphylaxis symptoms have begun. Plasma histamine levels also rises as soon as five to 10 minutes after onset but remain elevated for only 30 to 60 minutes.DIAGNOSTIC CRITERIAnaphylaxis network symposium: J Allergy Clin Immunol 2006 ;117 : 391-7

LAB INVESTIGATION

PREVENTION

TREATMENT-FIRST AID

TREATMENT OF ANAPHYLAXISEPINEPHRINE (1:1000) SC or IM- 0.01 mg/kg (maximal dose 0.3-0.5 ml)- administer in a proximal extremity- may repeat every 10-15 min, p.r.n.EPINEPHRINE intravenously (IV)- used for anaphylactic shock not responding to therapy- monitor for cardiac arrhythmiasEPINEPHRINE via endotracheal tubeEpi-pen shold be kept at work, homeIncase of children,it should be kept in school as well.

TREATMENT OF ANAPHYLAXISBenadryl (diphenhydramine)- H1 antagonist

Tagamet (cimetidine)- H2 antagonist

Corticosteroid therapy: hydrocortisone IV or prednisone po

TREATMENT OF ANAPHYLAXISBiphasic courses in some cases of anaphylaxis: Recurrence of symptoms: 1-8 hrs laterIn those with severe anaphylaxis, observe for 6 hours or longer.In milder cases, treat with prednisone; Benadryl every 4 to 6 hours; advise to return immediately for recurrent symptoms

TREATMENT OF ANAPHYLAXIS IN BETA BLOCKED PATIENTSGive epinephrine initially.If patient does not respond to epinephrine and other usual therapyGlucagon 1 mg IV over 2 minutes

USE OF EPINEPHRINE INFOOD ALLERGYEpinephrine should be used immediately after accidental ingestion of foods that have caused anaphylactic reactions in the past.An individual who is allergic to peanut, nuts**, shellfish, and fish should immediately take epinephrine if they consume one of these foods.A mild allergic reaction to other foods (e.g. minor hives,vomiting) may be treated with an antihistamine

ReferencesAbbas & Lichtman, Basic Immunology 3E, Chapter 11http://www.authorstream.com/Presentation/Moiloa-898248-anaphylaxis/http://med.mui.ac.ir/clinical/orjanc/Anaphylaxis.ppthttp://www.uptodate.com/contents/anaphylaxis-symptoms-and-diagnosis-beyond-the-basicshttp://www.oregonems.org/Downloads/Anaphylaxis.pptAnaphylaxis network symposium: J Allergy Clin Immunol 2006 ;117 : 391-7

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