AIT and AD: OVERVIEW OF THE EVIDENCE
A large number of clinical studies were published to assess the clinical effectiveness of SCIT and SLIT in children with AD. Both routes of administration, subcutaneous (SCIT) or sublingual (SLIT), have been studied in AD and have been equally demonstrated to work through similar mechanisms.
The first encouraging study on applying SCIT in AD was published in 1974 by Kaufman and Roth.5 Until the 2000s, several double-blind or not blind, randomized or not, placebo-controlled studies showed positive results on the efficacy of SCIT in children, but were conducted on small study’s size.5,6 In 2015 Lee et al.6 retrospectively assessed 217 AD patients, aged 13-29 years old, treated with SCIT for at least three years. They observed the improvement of skin disease in 88.4% out of patients, a better outcome in patients younger than 12 years of age, in moderate/severe HDM AD. Also, Nahm et al.6 described in an observational cohort study a favorable clinical response in 73.6% out of 251 patients, aged between 5 and 55, treated with HDM SCIT for 12 months.
In the 1990s, SLIT represented a significant step forward, particularly suitable for pediatric patients. Galli et al.5,6carried out the first placebo-controlled study using oral AIT in 60 children with AD sensitized to HDM. After three years of HDM oral AIT, the study did not reveal significant differences among groups.
The first double-blind, randomized placebo-controlled study was published in 2007 by Pajno G.B. et al.5,6 They treated with HDM SLIT 56 children between 5 and 16 years old for 18 months. Among them, 28 children took SLIT in addition to standard therapy. A significant result was noticed in patients with mild-moderate AD, and, after nine months of treatment, the SCORAD index and amount of conventional therapy decreased in the active group than in placebo one.
Most of the subsequent studies confirmed the safety and efficacy of SLIT, although they were conducted on not standardized targeted populations and different AIT protocol schedule.7
In recent years many attempts to perform systematic review and meta-analysis on AIT in AD were made with a controversial conclusion, and no possible recommendation could be stated. Tam et al.8 highlighted some methodological errors of the first meta-analysis conducted by Bae et al., due to the lack of blinding of outcome assessment, high post-randomization losses to follow-up, small study size, and inconsistency of findings allergens.5,8 Also, Lee et al. in 2015 analyzed the most relevant trials in the literature and suggested the need for objective qualifying criteria about type and number of allergens, duration and schedule of therapy (rush or ultra-rush protocol).9 Accordingly, Slavyanakaya et al., Cox et al., Ginsberg and Eichenfield did not warrant the use of AIT in children with AD and declared the need for well-designed RCTs that compare the efficacy of AIT with standard treatment in well-defined AD “phenotypes”.5, 10, 11 In this direction, Pajno et al. suggested that a more precise selection of clinical phenotypes (e.g., sensitization, comorbidity, cause-effect relationship between IgE-sensitization and AD exacerbation) may help to identify patients who could benefit from AIT.12 Ridolo et al. proposed at least three criteria to select AD patient eligible to start AIT as an add-on therapy:(a)sensitization to aeroallergens, proven by skin prick test and/or IgE assay;(b)AD flare-ups induced by exposure to aeroallergens;(c) standardized type product for AIT must be chosen.6
In conclusion, the most recent guideline from the American Academy of Dermatology concludes that data available do not support the recommendation for its use in AD.1 The Joint Task Force and The European Academy of Dermatology’s suggest that clinicians can consider AIT treatment in selected patients characterized by aeroallergen sensitization, prevalently HDM, severe AD, clinical exacerbation after exposure to the causative allergen.1,2