Dall’anafilassi si può guarire o si rischia per tutta la vita? Elena Battistini U.O. Pneumologia...

Dall’anafilassi si può guarire o si rischia per tutta la vita?

Elena BattistiniU.O. Pneumologia IRCCS G GASLINI

Advances in allergic skin disease, anaphylaxis, andhypersensitivity 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

• 7 BAMBINI ATOPICI• PRICK/RAST positivi per

il pesce• TOLLERANO (assumono

pesce senza problemi)• MESSI COMUNQUE A

DIETA DI ESCLUSIONE

• 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)

Larramendi C.H. et al Allergy 1992;47:490


Specific Oral Tolerance Induction


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


SOTI in children with very severe cow’s milk–inducedreactions :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

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


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• 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

At home treatment schedule: a slow increase phase (1)


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


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


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SOTI: Outcome at 1 year in treatment group

13 %

23%

54%

10%

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.


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.


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

Change in milk dose thresholdS

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(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.


• 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.


Towards a cure for food allergy

Allergen-specific immunotherapy

• Oral immunotherapy (OIT)• Sublingual immunotherapy

(SLIT)• Heat-denatured protein

exposure• Engineered recombinant

food protein

Allergen non-specific immunotherapy

• 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

Dall’anafilassi si può guarire o si rischia per tutta la vita? Elena Battistini U.O. Pneumologia...

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