Dall’anafilassi si può guarire o si
rischia per tutta la vita?
Elena Battistini
U.O. Pneumologia IRCCS G GASLINI
Advances in allergic skin disease, anaphylaxis, and
hypersensitivity reactions to foods, drugs and insects in 2008
• Insect venom hypersensitivity: Sublingual
immunotherapy to honeybee venom reduces
large local reactions in a pilot concept study.
• Drug allergy: A successful rapid
desensitization protocol is presented for
chemotherapeutic agents.
• Food allergy: Studies show promise for milk
oral immunotherapy.
Sicherer SH and Leung DYM J Allergy Clin Immunol 2009;123:319-27
Food-specific immunotherapy:
Past, present, and future
Avoidance of the offending
food
Wood R.A J Allergy Clin Immunol 2008;121:336-7.
DIFFICOLTÀ E RISCHI DELLA DIETA DI
ELIMINAZIONE
• Penalizzazione nutrizionale e sociale.
• Rischio di reazioni gravi per assunzioni
inavvertite (“alimenti nascosti”).
• Dipendenza psicologica dalla disponibilità
dell’adrenalina.
• Peggioramento dell’intolleranza da astensione
protratta?
Tommasini A 2007 IRCCS Burlo Garofolo
POSSIBLE CONSEQUENCES OF ELIMINATION DIETS IN
ASYMPTOMATIC IMMEDIATE HYPERSENSITIVITY TO FISH
DOPO L’INIZIO DELLA
DIETA SENZA PESCE…….
(2-9 anni)
a) Nessun miglioramento
della sintomatologia di
base
b) Ripetuti episodi di
anafilassi anche severi,
per esposizione fortuita
al pesce (inalatoria,
digestiva, contatto)
•
• 7 BAMBINI ATOPICI
• PRICK/RAST positivi per il
pesce
• TOLLERANO (assumono
pesce senza problemi)
• MESSI COMUNQUE A DIETA
DI ESCLUSIONE
Larramendi C.H. et al Allergy 1992;47:490
Food-specific immunotherapy:
Past, present, and future
Specific Oral Tolerance
Induction
Wood R.A J Allergy Clin Immunol 2008;121:336-7.
Food-specific immunotherapy: major
questions and concerns
• safety
• the potential to induce long-term
tolerance versus only transient
desensitization
• whether these treatments will be safe
and effective in those with the most
severe forms of food allergy
Wood R.A J Allergy Clin Immunol 2008;121:336-7.
SOTI in children with very severe cow’s milk–induced
reactions :enrollment of patients
•
•
•
•
children aged 5-17 years
milk specific IgE levels ≥ 85KUA/L
DBPCFC positive with ≤ 0.8 mL of whole milk
a positive hystory for at least 1 severe allergic
reaction ( class 4-5) after accidental exposure to
milk or dairy products
Longo G. J Allergy Clin Immunol 2008;121:343-7
Longo G. J Allergy Clin Immunol 2008;121:343-7
SOTI Protocol
• the SOTI process consisted of 2 phases
• the first phase took place in the hospital, with a
rapid increase in milk dosage
• all children were administered antihistamine
daily (oxatomide, 1 mg/kg per day)
• all had a venous line placed
• a complete emergency kit was always available
Longo G. J Allergy Clin Immunol 2008;121:343-7
Longo G. J Allergy Clin Immunol 2008;121:343-7
At home treatment schedule:
a slow increase phase (1)
• increasing by 1 mL every second day
• personalized for each subject, on the basis of the
frequency and severity of side effects and the
confidence of the parents
• written instructions for the gradual increase in milk
dose at home
• appropriate training to manage adverse reactions
• a dedicated telephone number available 24 hours
a day
Longo G. J Allergy Clin Immunol 2008;121:343-7
At home treatment schedule:
a slow increase phase (2)
• Each family in both groups was contacted by
means of telephone periodically
• Once home dosing reached 150 mL of whole
milk in a single dose, the patients were asked
to eat increasing amounts of dairy products
• Antihistamine treatment was continued at
home until the 150 mL single dose was
reached and then reduced over 4 weeks
Longo G. J Allergy Clin Immunol 2008;121:343-7
Failure of the SOTI
• Subjects were discontinued from the study because
of adverse reactions if they were severe (class 5) or
frequent despite decreasing dosage
• The SOTI was considered to have failed if the child did
not reach at least 5 mL of undiluted milk in a single
dose after 1 year or if participation was stopped for
adverse effects
Longo G. J Allergy Clin Immunol 2008;121:343-7
Longo G. J Allergy Clin Immunol 2008;121:343-7
SOTI: Outcome at 1 year in
treatment group
10%
23%
54%
13 %
Longo G. J Allergy Clin Immunol 2008;121:343-7
Clinical implications (1)
• Tolerance can be achieved through a
progressive increase in oral administration of
cow’s milk.
• Even a partial tolerance resulted in a striking
improvement in quality of life.
Longo G. J Allergy Clin Immunol 2008;121:343-7
Clinical implications (2)
• The risk of fatal anaphylaxis during SOTI
compared with the risk of fatal anaphylaxis
after accidental exposure in untreated
patients still needs to be determined on the
basis of larger numbers of patients and longer
follow-up periods.
• SOTI should be restricted to carefully selected
clinical contexts.
Longo G. J Allergy Clin Immunol 2008;121:343-7
A randomized, double-blind, placebo-controlled study
of milk oral immunotherapy for cow’s milk allergy
Skripak JM J Allergy Clin Immunol 2008;122:1154-60
Skripak JM J Allergy Clin Immunol2008;122:1154-60
Change in milk dose threshold
(p = .002)
(p= .16)
(p= .0003)
Food specific immunotherapy:
unanswered questions
•
•
•
•
•
route ( oral versus sublingual)
optimal dosing
duration of therapy
permanent tolerance
safety profile
Skripak JM J Allergy Clin Immunol 2008;122:1154-60.
Food-specific immunotherapy:
Past, present, and future
• There are so many unanswered questions that
it is safe to say that this treatment will not be
ready for general use for many years
• It is also entirely possible that other
approaches for the treatment of food allergy
will emerge as safer, more effective, or both.
Wood R.A J Allergy Clin Immunol 2008;121:336-7.
Towards a cure for food allergy
Allergen-specific immunotherapy
Allergen non-specific immunotherapy
• Oral immunotherapy (OIT)
• Sublingual immunotherapy
(SLIT)
• Heat-denatured protein
exposure
• Engineered recombinant
food protein
• Anti-IgE immunotherapy
• Chinese herbal medicine
(Food Allergy Herbal
Formulas -2)
• Strategies targeting specific
immune system molecules
or their receptors
Shripak M, Sampson HA Current Opinion in Immunology 2008, 20:690–6