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: Insect venom hypersensitivity: Sublingual immunotherapy to honeybee venom reduces large local reactions in a pilot concept study. Drug allergy: Drug allergy: A successful rapid desensitization protocol is presented for chemotherapeutic agents. Food allergy: 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, 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

Food-specific immunotherapy:, 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 safety long-term tolerance the potential to induce long-term tolerance versus only transient desensitization safe effective 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

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

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) 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 adverse reactions severe (class 5) frequent Subjects were discontinued from the study because of adverse reactions if they were severe (class 5) or frequent despite decreasing dosage at least 5 mL of undiluted milk 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

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. 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. carefully selected clinical contexts. 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:

Change in milk dose threshold Skripak JM J Allergy Clin Immunol2008;122: (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:

Food-specific immunotherapy:, and future Food-specific immunotherapy: Past, present, and future will not be ready 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 other approaches 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 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