1.1 Sublingual immunotherapy (SLIT) (Table S1)
Three studies, a RDBPC19 and a follow-up28 conducted by the same team, and a prospective cohort22, investigated SLIT for the treatment of PFA or LTP syndromes. The first two studies used hazelnut extract standardized in the major allergens Cor a 1 and Cor a 8 in 12 and 7 adults with hazelnut allergy, respectively. The third study investigated the effect of Pru p 3 SLIT in 29 children and adults with LTP syndrome, including 5 patients with almond allergy, 5 with walnut, 10 with hazelnut, and 1 with cashew allergy. Hazelnut studies required a DBPCFC at baseline, while the Pru p 3 study relied on history. The RDBPC study included 12 patients in placebo, the follow-up study used baseline assessment as the comparator, and the real-life cohort included 13 patients who followed the standard of care/avoidance (SOC). In all three studies, SLIT started with a build-up phase and gradual escalations until maintenance dose was reached (13,25 mg of total hazelnut protein, corresponding to 24,34 μg of Cor a 8 and 37,63 μg of Cor a 1 in the hazelnut-SLIT, and 12,5 μg of Pru p 3 in the Pru p 3-SLIT). The time of intervention varied from 8 weeks 19 to 1 year22. The primary outcome in all studies was the effectiveness of SLIT, and was assessed by the changes in Eliciting Dose (ED) during the exit DBPCFC19,28, or by OFCs to unpeeled peach and nuts22. Hazelnut SLIT19,28 was successful in increasing ED and induced immunological changes in a time-depended way. More than 50% of patients with PF- or LTP-allergy passed an exit DBPCFC to 20 gr of hazelnut after at least 8 weeks of treatment. On the contrary, the effectiveness of Pru p 3 SLIT for a year on LTP- allergy to hazelnut was assessed in only 3 of the 10 hazelnut allergic patients, and one of them passed an exit OFC to 14 gr of nut. This could be attributed to the lowest maintenance dose, or to the inability of Pru p 3 to cross-desensitize Cor a 822. Regarding safety, SLIT was mainly associated with oral pruritus. No epinephrine administrations were reported.
Because of the favorable safety profile, more studies are needed to investigate if SLIT could represent an effective option for desensitizing patients with PFAS or LTPS to tree nuts.