Miti e realtà:
Le allergie alimentari.
Alessandro Fiocchi
UOC Allergologia
OPBG
Roma, 28 ottobre 2014
Miti e realtà:
Le allergie alimentari.
Alessandro Fiocchi
UOC Allergologia
OPBG
Roma, 28 ottobre 2014
Miti & realtà in allergologia pediatrica
1. L’intolleranza alimentare
2. Il prick al bambino piccolo non si può fare
3. Le diete inutili e quelle pericolose
4. La OIT modifica la storia naturale dell'AA?
5. Conclusioni
The second wave
Respiratory allergy in westernized countries plateaued at the
beginning of this century
Warner JO. Anaphylaxis: the latest allergy epidemic. Pediatr Allergy Immunol 2007;18:1-2.
2nd wave emerged in the last 10-15 years
Prescott SL. Food Allergy: riding the second wave of the allergy epidemic.
PediatrAllergy Immunol 2011;22:155-60.
Particularly in preschool children….
Sicherer SH. Epidemiology of food allergy. J Allergy Clin Immunol 2011;127:594-602
… and in countries where respiratory allergy had increased, e.g.
UK, Australia and U.S.[
Food hypersensitivity
Food allergy
IgE-mediated food allergy
Nonallergic food hypersensitivity
Non-IgE-mediated food allergy
Johansson SGO. Revised nomenclature for allergy for global use:
Report of the Nomenclature of WAO
J Allergy Clin Immunol 2004; 113; 832-6
Symptom-based Clinical Score
(Cow's Milk Protein Intolerance Score)
Vandenplas Y.
Treatment of Cow's
Milk Protein Allergy.
Pediatr Gastroenterol
Hepatol Nutr.
2014;17:1-5
Symptoms Linked to food Allergies
Psoriasis
Haemorroids
SKIN: Acne, dermatitis, eczema, itching, psoriasis.
HEADACHES: various kinds including migraine.
Refractive
EYE CONDITIONS: conjunctivitis, eye pain, periods of blurred vision, sensitivity
to light, tearing,
changes
temporary refractive changes.
EAR CONDITIONS: hearing loss, infections, inflammations, Meniere’s syndrome, tinnitus, repeated
ear trouble.
CARDIOVASCULAR:
angina, high blood pressure, irregular heartbeat, low blood pressure, rapid pulse.
Bedwetting
GASTROINTESTINAL: constipation, diarrhoea, gall bladder pains, wind, gastric ulcer, gastro-intestinal
bleeding, heartburn, haemorrhoids, indigestion, mucous colitis, nausea, pains or cramps, spastic
colon, vomiting.
RESPIRATORY: asthma, chronic rhinitis, coughing, frequent "colds", hay fever, mouth breathing,
nosebleeds, postnasal discharge, sinusitis, stuffy nose, wheezing.
UROLOGICAL: bedwetting, frequent
night urination, frequent urination, painful or difficult urination.
Body odour
MUSCULO-SKELETAL: arthritis, joint pains, muscle cramps, muscle aches and pains, muscle spasms,
muscle weakness.
Overweight
MENTAL-BEHAVIOURAL: anxiety, delusions, depression (including psychotic),
dizzy spells, drowsiness,
epilepsy, floating sensations, general fatigue, hallucinations, hyperactivity, insomnia, irritability,
learning disorders, minimal brain dysfunction, nervousness, periods of confusion, phobias, poor
concentration, poor memory, poor muscle coordination, restlessness, schizophrenia, sleeps at
inappropriate times, sleeps too little, sleeps too much, tension-fatigue syndrome, unsteadiness.
OTHER: Abnormal body odour, excessive sweating, general weakness, hypoglycaemia, nightsweating, overweight, underweight, virus infections
http://www.foodallergycure.com/
Unnecessary milk elimination diets in children with
uncorrected diagnosis of CMA.
7%
van den Hoogen S.: Suspected cow’s milk allergy in everyday
general practice: a retrospective cohort study on health care burden
and guideline adherence. BMC Research Notes 2014 7:507.
Unnecessary milk elimination diets in
children with atopic dermatitis.
A positive CMA diagnosis
was rarely established after
adequate implementation and
reporting of diagnostics, yet
long term dietary measures
were prescribed in >7% of
patients.
0.8%
van den Hoogen S
Suspected cow’s milk
allergy in everyday
general practice: a
retrospective cohort
APLV
study
on health care
burden and guideline
@opbg.net
adherence. BMC
Research Notes 2014
7:507
Miti & realtà in allergologia pediatrica
1. L’intolleranza alimentare
2. Il prick al bambino piccolo non si può fare
3. Le diete inutili e quelle pericolose
4. La OIT modifica la storia naturale dell'AA?
5. Conclusioni
Allen KJ. Food allergy in childhood. Med J Aust. 2006; 185:394-400
Can PST be performed in infancy?
Ø SPT with histamine phosphate in 50% glycosaline (10 mg/dL)
Ø 297 histamine pricks in 210 patients
Whole
caseload
0-3
months
3-6
months
6-9
months
9-12
months
>12
months
n. Patients
210
12
26
39
35
98
Age (months)
22
2.55
4.25
7.86
10.34
33.17
Age SD (months)
24.47
0.77
1.59
1.21
0.79
8.19
histamine wheal Ø mean (mm)
5.016
3.82
4.58
5.06
4.76
5.36
Histamine wheal SD
1.56
0.87
0.72
1.62
1.5
1.79
Histamine wheal Ø range (mm)
2-12
3-5
3-5
2-12
3-8
3-12
Fiocchi A. Histamine reactivity dispels doubts about skin prick tests in infants.
Ann Allergy Asthma Immunol 2006; 97:46
Miti & realtà in allergologia pediatrica
1. L’intolleranza alimentare
2. Il prick al bambino piccolo non si può fare
3. Le diete inutili e quelle pericolose
4. La OIT modifica la storia naturale dell'AA?
5. Conclusioni
Nickel allergy.
a diet regimen for diagnosis
• Chocolate
• Potatoes
• Salmon
• Nuts and Legumes (beans, lentils)
• Any canned food or canned fruit
• Hot water from the tap
• Anything acidic (like tomatoes) cooked in a stainless steel pan
• Leafy green vegetables
Braga M. Systemic nickel allergy syndrome: nosologic framework and usefulness of diet
regimen for diagnosis. Int J Immunopathol Pharmacol. 2013; 26:707-16
Nickel allergy. Myth or reality?
a narrative overview
Nickel is the leading cause of ACD (Allergic Contact Dermatitis).
Systemic nickel allergy syndrome (SNAS) is very controversial.
No challenge studies
Nickel-related gastrointestinal symptoms
Nickel-related chronic fatigue syndrome
Nickel-related fibromyalgia
Nickel-related headache
Nickel-related recurring cold
Nickel-related recurrent infections
Nickel-related eczema
In the absence of genuine certainty,
we can only conclude that further and
broader studies, more rigorously
conducted, are needed.
Pizzutelli S. Systemic nickel hypersensitivity and diet: myth or reality?
Eur Ann Allergy Clin Immunol. 2011;43:5-18
Avoiding milk, dairy products, and egg
Alessandri C. Tolerability of a fully maturated cheese in cow's milk allergic
children: biochemical, immunochemical, and clinical aspects. PLoS One.
2012;7(7):e40945
CMA in toddlers
Jirillo F, Magrone T. Anti-inflammatory and anti-allergic properties of
donkey's and goat's milk. Endocr Metab Immune Disord Drug Targets.
2014 Mar;14(1):27-37
CMA in infants
Donkey’s milk
46 children with CMA
Median age: 24 mo. (mean: 36 mo.); range: 12-149 mo.
SPT with cow’s milk: positive 29/46
Soy allergy: 35/46
Challenge with cow’s milk : positive 41/46 (pear juice)
- anaphylaxis: 5
- within 1 h  16/41
- between 1 and 6 h  15/41
- after 6 h  18/41
Donkey’s milk tolerated in 82.6% of children
Reactions in immediate CMA: 7/33 (21.2%)
Monti G. Efficacy of donkey’s milk in treating highly problematic cow’s milk allergic
children: An in vivo and in vitro study. Pediatr Allergy Immunol 2007; 18:258-64
Extensively Hydrolysed Rice formulae
Risolac
Blemil Riso
Generalized edema more evident (A) in
the face and (B) in the legs (fovea sign)
APLV@
opbg.net
Novembre E. Severe hypoproteinemia in infant with AD.
Allergy. 2003;58:88-9
CMA in children with beef allergy, BA in children
with CMA
DBPCFC
Beef/milk
Milk/beef
100%
12 – 20%
Werfel SJ. Clinical reactivity to beef in children allergic to cow’s milk. J Allergy Clin
Immunol 1997;99:293-300
Martelli A. Allergy to cow’s milk in beef-allergic children.
Ann Allergy Asthma Immunol. 2002; 89S, 25-33
SDS-PAGE of commercially available lactose and
cow’s milk proteins
L
Lppt
BSA
-La
-Lg
-cas
-cas
k-cas
CM
Fiocchi A. Clinical tolerance to lactose in children
with cow's milk allergy. Pediatrics. 2003; 112:359-6
CMA in newborns
Miti & realtà in allergologia pediatrica
1. L’intolleranza alimentare
2. Il prick al bambino piccolo non si può fare
3. Le diete inutili e quelle pericolose
4. La OIT modifica la storia naturale dell'AA?
5. Conclusioni
Food allergy immunotherapy goals
Goals of treatment are two-fold:
1. Clinical desensitization - tolerate more food on treatment than
before starting
2. Eventual clinical tolerance - off treatment can tolerate food –how
long off treatment?
no good definition of tolerance –issue in all of allergic diseases
“sustained unresponsiveness” –
Burks AW, CoFAR. Oral immunotherapy for treatment of egg allergy in children. N
Engl J Med. 2012 Jul 19;367:233-43
SPT mean wheal size decrease by 6 mo
Further decrease to 24 mo
Specific-IgG4 increase by 2-3 mo
Continue to increase to 24 mo, then
Basophil activation decreased by 4 mo
begin
to decline
Specific-IgE
increase
by 2-3 mo.
Further
decreased
to 24 mo
Decrease by 24 mo
Effector Cells
Specific-IgE
Specific-IgG4
0
2
3
4
6
9
12
18
Time on OIT (months)
Courtesy of Wesley Burks
24
36
Probability of persistent peanut allergy
Peanut Allergy Natural history
1.00
0.75
0.50
Kaplan-Meier analysis
N=267
0.25
0.00
0
Courtesy of David Hill
2
4
6
Age in years
8
10
Ho M,Wong W, Allen K JACI 2014
Months from diagnostic DBPCFC
Fiocchi A. Factors associated with cow's milk allergy outcomes in infant referrals:
the Milan Cow's Milk Allergy Cohort study. Ann Allergy Asthma Immunol
2008;101:166-73
Persistent CMA%
MiCMAC cohort: survival curve
Tolerance vs. desensitization
• Large number of studies evaluated the ability for OIT to
induce desensitization
• Few OIT studies have assessed for tolerance as a study
outcome:
- 3 uncontrolled open studies
- three RCTs
Tolerance vs. desensitization
•
•
•
•
Open study
23 children with peanut allergy
For 22 to 26 months
Tolerance 4/23 (17%)
Blumchen K, Ulbricht H, Staden U. Oral peanut immunotherapy in children with peanut
anaphylaxis. J Allergy Clin Immunol 2011: 126: 83–91.
Probability of persistent peanut allergy
Peanut allergy natural history
1.00
0.75
0.50
Kaplan-Meier analysis
N=267
0.25
0.00
0
2
4
6
8
10
Blumchen K, Ulbricht H, Staden U. Oral peanut immunotherapy in children with peanut anaphylaxis.
J Allergy Clin Immunol 2011: 126: 83–91.
Tolerance vs. desensitization
•
•
•
•
•
Open study
25 children with milk or egg allergy
For 11 to 59 months
Tolerance 9/25 (36%)
Control group tolerated 35%
Staden U. Specific oral tolerance induction in food allergy in children: efficacy and
clinical patterns of reaction. Allergy. 2007;62:1261-9
Tolerance vs. desensitization
SOTI-group (n=25)
Pattern
N (%)
I
Responder
9 (36)
II
Responder
(with regular daily intake)
3 (12)
III
Partial responder
4 (16)
IV
Non responder
9 (36)
Staden U. Specific oral tolerance induction in food allergy in children: efficacy and
clinical patterns of reaction. Allergy. 2007;62:1261-9
Tolerance vs. desensitization
SOTI-group (n=25)
Control-group (n=20)
Pattern
N (%)
Result
N (%)
Tolerant
7 (35)
Allergic
13 (65)
I
Responder (natural corse or
SOTI?)
9 (36)
II
Responder
(with regular daily intake)
3 (12)
III
Partial responder
4 (16)
IV
Non responder
9 (36)
Staden U. Specific oral tolerance induction in food allergy in children: efficacy and
clinical patterns of reaction. Allergy. 2007;62:1261-9
Miti & realtà in allergologia pediatrica
1. L’intolleranza alimentare
2. Il prick al bambino piccolo non si può fare
3. Le diete inutili e quelle pericolose
4. La OIT modifica la storia naturale dell'AA?
5. Conclusioni
Food allergens accused
• Years ago, they were found guilty.
• Convicted largely circumstantial evidence, and sent into exile.
• They were exiled from the diets of small children all around the
world.
Prescott S, Fiocchi A. Avoidance or exposure to foods in prevention and treatment of food
allergy? Curr Opin Allergy Clin Immunol 2010,10:258–66
Allergia alla fragola
Act II, Scene IV – The London Tower
Gloucester: “My Lord of Ely, when I was last in Holborn
I saw good strawberries in your garden there.
I do beseech you send for more of them”
……….
Ely: “Where is my Lord, the Duke of Gloucester?
I have sent for these strawberries”.
……….
Gloucester: “…thou conspired my death with devilish plots!
Then be your eyes the witness of their evil
Look how I am bewitch’d; behold, mine arm
Is llike a blasted sapling wither’d up”
William Shakespeare, King Richard the Third, 1592
Allergie frequenti?.....
36 lavori
2008 lavori
Cortesia di Alberto Martelli
Allergie rare?.....
Allergie impossibili?.....
Fiocchi A. Litchi chinensis allergy in a boy. Annals Allergy
Asthma Immunol 2004; 92: 51-2
Astier C . First case report of anaphylaxis to quinoa, a novel
food in France. Allergy 2009;64:819-20
Allergie impossibili?.....
-
A twelve-year boy
allergic rhinitis to grass pollen, cat, house-dust mite
OAS for apple, watermelon
sneezing after smelling and eating a small amount of risotto
SPT with rice negative
saffron powder SPT positive
Total IgE  2,872;
ImmunoCAP  10.1 kU/L to saffron and 2 kU/L to rice.
Fiocchi A. Spice allergies can happen also in children. Annals
Allergy Asthma Immunol 2014; 112: 43-4
DBPCFEC
DBPCFC with PLC in resting conditions and the food-exercise test
after the meal → negative
DBPCFEC was after the meal containing 1 ml of mould solution
→ positive
Fiocchi A. Exercise-induced anaphylaxis following food-contaminant ingestion at Double-Blinded,
Placebo-Controlled, Food Exercise Challenge. J Allergy Clin Immunol 1997; 100:424-25