Management of Anaphylaxis

Controversial dogmaControversial dogma

Dr Peter Arkwright

Senior Lecturer in Paediatric Allergy and Immunology

Royal Manchester Children’s Hospital

• Adrenaline

– Position

– Number

• Avoidance

Dogma in the dock

• Avoidance

– versus exposure

– gut versus skin

• first line treatment for anaphylaxis

• for food and venom associated

anaphylaxis, recommended route is

Adrenaline

anaphylaxis, recommended route is

intramuscular, not subcutaneous or

intravenous

Concernincrease obesity in society

with the increasing levels of obesity will auto-

injectors still deliver adrenaline into the

muscle?muscle?

2011 Overweight or obese Obese

>30 kg/m2

Men 65 24

Women 58 26

Children 30 16

• skin to muscle depth was measured by ultrasound at set

distances down the thigh and leg in 93 children attending the

paediatric allergy clinic at RMCH

• weight, height and waist circumference were measured and

BMI calculated Bewick et al, JACI IP, 2013

• age 1 to 16 years old, median 6 years

• 56% male

• 64% White, 24% Asian

• overweight 9%, obese 17%

Results

• overweight 9%, obese 17%

20

30

40

mu

scle

th

ick

ne

ss>

ne

ed

le le

ng

th

12 (9–17)mm

9 (7–13)mm

% children with SC thickness > needle length

0

10

20

1/4 from hip mid thigh 3/4 from hip mid calf

% w

ith

sk

in-m

usc

le t

hic

kn

ess

>n

ee

dle

len

gth

8 (7–10)mm

8 (7–10)mm

Needle length: Junior 12.7mm, Adult 15.9mm n = 93

50

75

100

% of children with skin to muscle thickness > needle length

Green – healthy weight

Yellow – overweight (85-94th C)

Red – obese (>95th C)gender/age specific BMI

2000 CDC growth charts

% s

kin

to

mu

scle

th

ick

ne

ss >

ne

ed

le le

ng

th

0

25

50

n = 93

% s

kin

to

mu

scle

th

ick

ne

ss >

ne

ed

le le

ng

th

1/4 from hip mid calf3/4 from hipmid thigh

age and gender are not independent determinants

• 120 adults, aged 18 - 55 years old

• mid-thigh measurements only

• mean BMI 29.2 kg/m2

• 31% potential failure risk (women 55% vs men

Bhalla et al, Ohio study in adults

• 31% potential failure risk (women 55% vs men

5%)

Bhalla et al, Am J Emerg Med, 2013

• review of records 4 New England Hospitals 2001

– 2006 of ED patients presenting with allergic

reactions

• 18% overweight, 22% obese

Rudders et al, New England retrospective

review

• 18% overweight, 22% obese

• 321 (261 children and 60 adults) received

adrenaline: 267 1 dose; 54 2+ doses

• obese patients or women were no more likely to

receive 2 doses

• nor were those with respiratory symptomsRudders et al, JACI, 2012

• Obesity in both children and adults is

associated with an increased risk that

adrenaline will not be injected into the muscle

• Does it matter? If it did one might expect

Conclusions

• Does it matter? If it did one might expect

more second doses, hospital admissions and

deaths in obese and in women.

• In more obese children consider injector in

lower half of thigh

• AC is recommending TWO devices

• clinicians vary in the number of auto-injectors

they prescribe

Number of prescribed auto-injectors

Number of pens in

children with food allergyMt Sinai Hospital

New York

RMCH

Manchester

number of children 413, median 4.5 y

pea/tree nuts, milk

84% had auto-injectors

prescribed

298, median 10 y

pea/tree nuts, milk

100% had auto-injectors,

95% had 2+ devices

Jarvinen et al, JACI, 2008

Arkwright, JACI 2009

prescribed 95% had 2+ devices

Number requiring auto-injector

1 dose 71 (19%)

50% by non-meds

18 (6%)

2 doses 18 (4%) egg - restaurant

1 by non-med

0

• auto-injectors should never be prescribed

without concomitant training on how and

when to use the device

• decision on the number of auto-injectors

Discussion

• decision on the number of auto-injectors

should be based on evidence and need

• variables include: peer-reviewed published

evidence, family’s requirements, residential

location, travel

• Is strict avoidance of foods that children are

partly tolerant to making their food allergies

– more severe?

Controversy

– more severe?

– more prolonged?

Egg

NATURAL HISTORY OF CHILDREN WHO TOLERATE BAKED MILK AND EGG

0

Milk

Pro

ba

bil

ity

of

de

ve

lop

ing

to

lera

nce

Challenge: baked milk muffin

1.3g of dry milk powder

cooked 180C for 30 min

Challenge: baked egg muffin

2.2g of dry milk powder

cooked 180C for 30 min

Kim JS et al, JACI, 2011, n = 88

¾ of children tolerated baked milk challenge

8X more likely to develop tolerance to fresh milk

Leonard SA et al, JACI, 2012, n = 79

Time to mean scrambled egg tolerance

3½ versus 5 years

Pro

ba

bil

ity

of

de

ve

lop

ing

to

lera

nce

MMonths following first visit

Pro

ba

bil

ity

of

de

ve

lop

ing

to

lera

nce

Milk Egg

Baked food

Complete avoidance

CURING MILK AND EGG ALLERGY WITH BAKED FOODS

Baked milk muffin

1.3g of dry milk powder

cooked 180C for 30 min

Baked egg muffin

2.2g of egg protein

cooked 180C for 30 min

MMonths following first visit

Pro

ba

bil

ity

of

de

ve

lop

ing

to

lera

nce

Leonard SA et al, JACI, 2012, n = 79

Children eating baked egg were 15X more

likely to develop tolerance to scrambled egg

Kim JS et al, JACI, 2011, n = 88

Children eating baked milk were 4X more

likely to develop tolerance to fresh milk

Standard advice

• Children with immediate cow’s milk or egg

allergy should avoid these foods in all forms

unless otherwise advised by an allergy

specialistspecialist

• Addition of dietary baked milk and egg is safe,

convenient and well-accepted by many

patients with milk and egg allergy

• Recommending baked milk and egg products

Evidence-based advice

• Recommending baked milk and egg products

to milk and egg allergic children represents an

important shift in the treatment paradigm for

these allergies

JACI, 2011

Palmar hyperlinearity(excessive lines on palms)

filaggrin

Filaggrin – gene involved in skin barrier

Clinical Associations

Atopic dermatitis*

0% (0/13) no mutation

44% (13/29) one mutation

76% (16/21) two mutation

Allergic asthmaSeverity (FEV1 & medication use)

only if associated with AD

(Palmer et al, JACI, 2007)76% (16/21) two mutation

(Palmer et al, Nat Genet, 2006)

(Winge et al, Br J Dermatol, 2011)

Peanut allergyRelative risk 5.3 (2.8 – 10.2)

(Brown et al, JACI, 2011)

*overall FLG mutations found in

20-40% of patients with moderate

to severe AD of Northern European

& Asian descent, but rare in Africans

relative risk 10.1 in patients with

erythema herpeticum

Tolerance

Allergy

GUT SKIN

• Age

• Severe asthma

• Genetic factors

Risk factors for severe and complex allergies

• Genetic factors

• Unnecessary food avoidance

• Adrenaline auto-injectors– increasing obesity in the community is increasing the

potential for more injections not being delivered into the muscle

– critical to ensure that auto-injectors are only prescribed to patients and carers that are adequately training in their use,

Points for discussion

patients and carers that are adequately training in their use, rather than prescribing additional pens in case of misfiring because of lack of training

• Avoidance– there is increasing evidence that complete avoidance of milk

and egg can prolong and exacerbate these allergies

– Ongoing studies e.g. LEAP will help to answer whether this is also the case for other foods e.g. peanut