ANAPHYLAXIS. Dr. Peter Lee

A

NAPHYLAXIS

O

BJECTIVES

1. To be able to define and diagnose anaphylaxis

2. Describe signs and symptoms

3. Identify patients at high risk for fatal reactions

4. Review management

1. Familiarization of treatment of specific cases of

W

HICH OF THE FOLLOWING MAY BE A SIGN OR SYMPTOM OF AN ACUTE

(

ANAPHYLACTIC

)

REACTION

?

A. Dyspnea

B. Angioedema of tongue

C. Menstrual cramping and bleeding

D. Chest Pain

E. A and B

W

HICH OF THE FOLLOWING MAY BE A SIGN OR SYMPTOM OF AN ACUTE

(

ANAPHYLACTIC

)

REACTION

?

A. Dyspnea

B. Angioedema of tongue

C. Menstrual cramping and bleeding

D. Chest Pain

E. A and B

W

HICH OF THE

F

OLLOWING IS A RISK

(

S

)

FACTOR FOR SEVERE OR FATAL

ANAPHYLAXIS

?

A. Asthma

B. ACEI

C. Beta blockers

D. A and C

W

HICH OF THE

F

OLLOWING IS A RISK

(

S

)

FACTOR FOR SEVERE OR FATAL

ANAPHYLAXIS

?

A. Asthma

B. ACEI

C. Beta blockers

D. A and C

W

HEN SHOULD A CHILD WITH

ANAPHYLAXIS SWITCH FROM A

0.15

MG TO

0.30

MG AUTOINJECTOR

?

A. 20kg B. 25kg C. 30kg D. 35kg

W

HEN SHOULD A CHILD WITH

ANAPHYLAXIS SWITCH FROM A

0.15

MG TO

0.30

MG AUTOINJECTOR

?

A. 20kg

B. 25kg

C. 30kg D. 35kg

ANAPHYLAXIS:

DEFINITION

(SAMPSON JACI 2006;117:391)

|

“

Anaphylaxis is a

serious allergic reaction

that is rapid in onset

ANAPHYLAXIS IS HIGHLY LIKELY WHEN ANY ONE OF

THE FOLLOWING THREE CRITERIA ARE FULFILLED:

[SAMPSON ET ALJACI 2006;117:391]

1. Acute onset of an illness (minutes to hours) with involvement of the skin and/or mucosal tissue; and at least one of the following:

a. Respiratory compromise b. Reduced blood pressure

ANAPHYLAXIS IS HIGHLY LIKELY WHEN ANY ONE OF

THE FOLLOWING THREE CRITERIA ARE FULFILLED:

[SAMPSON ET ALJACI 2006;117:391]

2. Two or more of the following that occur

rapidly after exposure to a

likely

allergen for that patient:

a)

Involvement of the skin/mucosal tissue

(hives, itch/flush, angioedema)

b)

Respiratory compromise

c)

Reduced BP or associated symptoms

d)

Persistent GI symptoms

ANAPHYLAXIS IS HIGHLY LIKELY WHEN ANY ONE OF

THE FOLLOWING THREE CRITERIA ARE FULFILLED:

[SAMPSON ET ALJACI 2006;117:391]

3. Reduced BP following exposure to a known

allergen for that patient.

a. Infants and children: low systolic BP (age specific) or >30% drop in systolic BP.

<70mmHg from 1m to 1 year

<70mmHg + [2xage] from 1-10 years

b. Adults: systolic BP <90mmHg or >30% drop from the individual’s baseline.

I

G

E-

DEPENDENT

R

ELEASE OF

I

NFLAMMATORY

M

EDIATORS

Immediate Release Granule contents: Histamine, TNF‐α,  Proteases, Heparin Over Minutes Lipid mediators:  Prostaglandins Leukotrienes Over Hours Cytokine production: Specifically TNF‐α, IL‐4, IL‐13 IgE FcεRI FcεRI binding site Cell recruitment Sneezing  Nasal congestion Itchy, runny nose Watery eyes

Wheezing

S

YMPTOMS

/S

IGNS OF

A

NAPHYLAXIS

Oral: Pruritus of lips, tongue, and palate; edema of lips and tongue

Cutaneous: Flushing, pruritus, urticaria, angioedema

Rhinoconjunctivitis: Pruritus, congestion,

rhinorrhea, and sneezing, periorbital pruritus,

erythema, and edema; conjunctival erythema and tearing

S

YMPTOMS

/S

IGNS OF

A

NAPHYLAXIS

|

Laryngeal: Pruritus and “tightness” in the

throat, dysphagia, dysphonia and

hoarseness/stridor, cough, and sensation

of itching in the external auditory canals

|

Respiratory: Dyspnea, chest tightness,

S

YMPTOMS

/S

IGNS OF

A

NAPHYLAXIS

Gastrointestinal: Nausea, abdominal pain (colicky), vomiting and diarrhea

Cardiovascular: Hypotension, syncope, chest pain, dysrhythmia

S

YMPTOMS

/S

IGNS OF

A

NAPHYLAXIS

|

Other: lower back pain and

uterine contractions/bleeding in

women; aura of impending

M

OST

F

REQUENT

S

IGNS AND

S

YMPTOMS OF

A

NAPHYLAXIS

Manifestation Percent

Urticaria/angioedema 88

Upper airway edema 56

Dyspnea/wheeze 47

Flush 46

Hypotension 10-33

W

HAT IS THE

C

LINICAL

C

OURSE OF

A

NAPHYLAXIS

?

Uniphasic

Time Initial symptoms Treatment Allergen exposure Symptom intensity

W

HAT IS THE

C

LINICAL

C

OURSE OF

A

NAPHYLAXIS

?

Biphasic

Time Initial symptoms Treatment Allergen exposure 2nd _phase symptoms Treatment 1-72 hours Symptom intensity

W

HAT IS THE

C

LINICAL

C

OURSE OF

A

NAPHYLAXIS

?

Protracted

Time Initial symptoms Allergen exposure Possibly > 24 hours Symptom intensity

R

ISK

F

ACTORS FOR

D

EVELOPMENT OF

F

OOD

A

LLERGY

| Genetics

| Race

y Increased in Asians1 and African-Americans2

| Sex2

| Increased hygiene

| Vit. D

| Reduced consumption of

omega-3-polyunsaturated fatty acids3

| Antacids4

| Route of exposure5 and timing of exposure6,7

| Microbial factors8,9,

1. Koplin Allergy 2012; 2. Liu JACI 2010; 3 Kull Allergy 2006

4. Untersmayr FASEBJ 2005; 5. Lack NEJM 2003; 6 Katz JACI 2010

7. Du Toit JACI 2008; 8. Sudo J Immulo 1997; 9. Bager Clin Exp Allergy 2008

R

ISK

F

ACTORS FOR

D

EVELOPMENT OF

F

OOD

A

LLERGY

| Vitamin D

y <15 ng/mL increased risk of peanut sensitization1 y Higher rates of peanut and egg allergy in regions

farther from equator2

y Season of birth a risk factor3

y Vit. D sufficiency protective against food allergy 4

y However increased maternal Vit D levels also shown

to increase food allergy5

1. Sharief JACI 2011 2. Osboune JACI 2012 3. Vassallo JACI 2010 4. Allen JACI 2013 5. Weisee Allergy 2013

W

HAT

T

RIGGERS ANAPHYLAXIS

?

0 5 10 15 20 25 30 35

Food Drug/Bio Insect Sting Idiopathic Exercise Allergen

Vaccines 35 20 ₂₀ 20 5 3 % of Cases Golden 2004 Golden.Anaphylaxis, 2004

A

NAPHYLAXIS

-

RELATED

M

ORTALITY

| Data are scarce on mortality due to anaphylaxis

y under-reporting is a problem1

| Estimated incidence of fatal anaphylaxis 0.3-1/million

people/year2,3

| Deaths from upper airway edema, respiratory failure or

cardiovascular collapse

1. Simons JACI 2010

2. Pumphrey Curr Opin Allergy Clin Immnulogy 2004 3. Low Pathology 2006

F

ATAL

R

EACTIONS FROM

F

OOD

A

LLERGY

R

ISK

F

ACTORS FOR SEVERE OR FATAL

A

NAPHYLAXIS

| Biphasic reaction

| Cutaneous symptoms not present

| Underlying asthma (especially poorly controlled) | Cardiopulmonary diseases

| Delayed epinephrine | Symptom denial

| Previous severe reaction | Adolescents, young adults | Beta blockers/ACEI

| Underlying mastocytosis

| Key foods: peanuts and tree nuts dominate (~90%

of fatalities), fish, crustaceans

A

NAPHYLAXIS

:D

IAGNOSIS

| Serum tryptase

y Draw during 1st 1-2 hours y Peak 60-90 minutes

F

UTURE

I

NVESTIGATIONS

1. Skin tests

2. Blood tests

M

ANAGEMENT OF

A

NAPHYLAXIS

1. EPINEPHRINE IS ALWAYS FIRST!

2. Always lay patient in supine position legs

elevated

3. Maintain airway, supplement O2

4. Large volume fluid resuscitation (if possible)

1. Up to 35% shift in IVV within minutes

5. Other agents

E

PINEPHRINE

| Epinephrine is the drug of choice for anaphylaxis

y available in auto-injector which is simple to use and

gives reliable results

y reverses associated hypotension and bronchospasm

| Fatality rates are highest in patients in whom

treatment with epinephrine is delayed

| There are no absolute contraindications to epinephrine

administration in the setting of anaphylaxis

| Antihistamines must not be used as first-line treatment for anaphylactic reactions

O'Dowd SC, et al. Anaphylaxis in Adults. Available at: www.uptodate.com 2006.

Sampson HA, et al. N Engl J Med 1992; 327(6):380-4. Sicherer SH, et al. JACI 2005; 115(3):575-83.

E

PINEPHRINE

| IM Epinephrine

y Adults 0.3-0.5mL of 1mg/mL (1:1000) anterolateral thigh y Children 0.01mL (mg)/kg max 0.5mL

y May need to repeat q5-15 minutes

| Auto-injectors (intramuscular injection in the anterolateral thigh)

| Two epinephrine auto-injectors available: EpiPen /Allerject

0.3 mg and EpiPen Jr./Allerject 0.15 mg

| Children weighing 15 kg - 30 kg might be under-treated with

“junior” dosing; NIH recommends switch at 25kg

| Second dose of epinephrine may be required

IM vs SQ Epinephrine

IM vs SQ Epinephrine

Simons FER: J Allergy Clin Immunol 2004;113:837-44

0 10 20 30 40 Subcutaneous epinephrine Intramuscular epinephrine 0 10 20 30 40 Subcutaneous epinephrine Intramuscular epinephrine (Epipen®) (Epipen®)

Time to C_max after injection (minutes) Time to C_max after injection (minutes)

8 +/- 2 minutes 8 +/- 2 minutes + + --34 14 (5 – 120) minutes p < 0.05 34 14 (5 – 120) minutes p < 0.05 --+ +

O

THER

A

GENTS

| Diphenhydramine 25-50mg IV or oral OR

cetirizine 10mg

y Only helpful for itch and urticaria y Continue for 2-3 days

| Ranitidine 50mg IV or 150mg PO

| Bronchodilators

| Corticosteroids

y Continue for 3 days

I

NADEQUATE

M

ANAGEMENT OF

A

NAPHYLAXIS

| Survey of 1000 US patients

y Treatment of past reactions | Only 11% received epi

y Treatment of future reactions

| 52% never received auto injector prescription | 60% no epi available

| 37% planned to use antihistamine | 34% planned to use autoinjector

| Overall prevalence 1.6% in adults

P

ATIENT

A

CTION

P

LAN

| Describe the signs and symptoms of anaphylaxis

| Instruct on when and how to use epinephrine

y Training for caregivers, family, friends etc

| Instruct patient to give epinephrine immediately

(no contraindication to the use of epinephrine in a life-threatening situation such as anaphylaxis)

| Call 911

| List emergency contact information

E

XAMPLE OF AN

A

NAPHYLAXIS

P

ATIENT

A

CTION

P

LAN

Shown: Action plan for schools recommended by the CSACI. Available at:

http://www.anaphylaxis.ca/en/educators/educator_resourc es.html

M

Y

C

HILD ONLY HAD A MILD REACTION

,

DO

I

NEED TO CARRY AN

E

PIPEN

?

H

OW

Q

UICKLY

S

HOULD

E

PINEPHRINE BE

A

VAILABLE

?

1. Pumphrey Clin Exp Allergy. 2000;30:1144–1150 Minutes to Arrest First Epinephrine

Median Range None Before After

Iatrogenic 55 5 1-80 6 9 40

Food 37 30 6-360 13 8 16

I

S

S

KIN

C

ONTACT WITH

A

LLERGEN

H

ARMFUL

?

| One gram of peanut butter was applied directly

to the skin of 281 children with peanut allergy

| 330 tests for peanut contact sensitivity were

performed; 136 (41%) were positive.

| No child had a systemic reaction following topical

application of peanut butter.

W

HAT ABOUT

I

NHALATION

?

| 33 children with significant peanut allergy

| Inhalation (surface area of 6.3 square inches 12

inches from the face for 10 minutes)

y scent was masked with soy butter, tuna, and mint

(inhalation).

| None experienced a systemic or respiratory

reaction.

H

OW CLEAN DO EATING SURFACES NEED TO BE

?

H

OW MANY DOES OF EPINEPHRINE SHOULD BE AVAILABLE

?

| 13% required two doses1

| 6% required three doses

| Peanuts, tree nuts, cow’s milk accounted for 75%

of reactions requiring epinephrine

| Patients should carry 2 doses (2010 Guidelines)2

Jarvinen JACI 2008;122:133-8 Bocye JACI 2010

M

Y

E

PI

P

EN HAS EXPIRED

,

BUT HASN

’

T CHANGED COLOR

,

CAN

I

KEEP USING IT

?

W

HEN SHOULD EPINEPHRINE BE GIVEN

?

| As early as possible after the onset of symptoms

of a severe allergic reaction

| For people with a history of a severe

cardiovascular collapse on exposure to an allergen, the physician may advise that

epinephrine be administered immediately after exposure to that allergen, and before any reaction has begun

It is ALWAYS better to give

epinephrine if in doubt

V

ENOM ALLERGY

: C

RITERIA FOR

I

MMUNOTHERAPY

| All patients with a systemic allergic reaction with

a positive skin or RAST

y VIT generally not required for children < or = 16 with

cutaneous systemic reactions only

y VIT generally not necessary who have large local

reactions, although consider in those with unavoidable exposures

| VIT reduces risk of anaphylaxis from up to 70%

O

RAL

I

MMUNOTHERAPY FOR FOOD ALLERGY

| Oral immunotherapy reported for many foods

cow’s milk, egg, fish apple, orange, celery and peanut

| Start at a small dose and advancing to a higher

STOP II(

STUDY OF TOLERANCE TO

PEANUT

)

| 75/85 (88%) able to tolerate 800 mg peanut protein daily | 49/85 (58%) able to tolerate 1400 mg challenge at 26 weeks | Main adverse events:

y Mouth itch 81%

y Abdominal pain 57% y Nausea/vomiting 33% y Wheezing 24%

y 2 doses of epi given during trial

| Withdrawals

y 5 withdrew because of symptoms y 1 withdrew because to taste

OIT

| Problems

y Desensitization versus tolerance y What do about missed doses

y Reactions to previously tolerated dose: physical

exertion after dosing, dosing on an empty stomach, dosing during menses, concurrent febrile illness, and having suboptimally controlled asthma

| Anaphylaxis in 7/1692 doses, one at maint at dose 3541 y Eosinophilic esophagitis

| OIT is INVESTIGATIONAL

S

UMMARY

: K

EY

P

OINTS IN MANAGING AND COUNSELING PATIENTS

| Anaphylaxis is unpredictable

y Patient should have action plan

| Epinephrine is always the drug of choice

y Use without delay

y Antihistamines or inhalers are NEVER 1st line

treatment

| Make sure your patient knows how use auto

injector

| Make sure auto injectors are up to date

| Two doses of epinephrine should be immediately

available

| All patients with suspected anaphylaxis should

R

ISK OF

S

YSTEMIC

R

EACTION IN

U

NTREATED

S

KIN

T

EST

P

OSITIVE

P

ATIENTS

Original Sting Reaction Risk of Systemic Reaction Severity Age 1 - 9 yrs 10 - 20 yrs Large local All 10 % 10 % Cutaneous Child 10 % 5 % systemic Adult 20 % 10 % Anaphylaxis Child 40 % 30 %

E

NCHANCED FOOD LABELLING

(A

UGUST

4

2012)

FOR MAIN INGREDIENTS

)

| Must say contains:

| almonds, Brazil nuts, cashews, hazelnuts, macadamia nuts,

pecans, pine nuts, pistachios or walnuts;

| peanuts; | sesame seeds; | wheat or triticale; | eggs; | milk; | soybeans; | crustaceans; | shellfish; | fish; or | mustard seeds

H

YGIENE

H

YPOTHESIS

| Epidemiology:

1. Endotoxin exposure is associated with less atopic sensitization, less AR, less atopic asthma in a dose dependant manner1

2. Pet ownership (>2 dogs or >2cats) is associated with less atopy at age 6-72

3. More older siblings or attending daycare at an early age (<6m) associated with less wheezing at ages

6,8,11,133

4. Serologic evidence of Toxoplasmosis, HSV1, hepatitis A associated with less atopy, AR and asthma4

5. Atopic infants have less enterococci, bifidobacteria and more clostridia and S. Aureus5

1 . Braun-Fahrlander, NEJM 2002 2. Ownby JAMA 2003

3. Ball, Arch Ped Adolec Med 2002 4. Matricardi JACI 2002

S

PECIFIC

I

G

E L

EVELS

A

SSOCIATED

WITH

95% R

ISK OF

R

EACTION

Age Group

Food

Serum IgE (kU/L)

Child

Egg

≥ 7

<2 years

Egg

≥ 2

Child

Cow Milk

≥ 15

<2 years

Cow Milk

≥ 5

Child

Peanut

≥ 14

Child

Fish

≥ 20

Sampson H. J Allergy Clin Immunol 2004;113:805‐19

Garcia‐Ara C, et al. J Allergy Clin Immunol 2001;107(1);185‐ 90

E

STIMATED

P

REVALENCE OF

F

OOD

A

LLERGY

Food

Children (%)

Adults (%)

Cow’s milk

2.5

0.3

Egg

1.3

0.2

Soy

0.3-0.4

0.04

Peanut

0.8

0.6

Tree nut

0.2

0.5

Crustaceans

Fish

0.1

0.1

2.0

0.4