Introduction
Nearly 30% of the adult population of Sweden report allergic rhinitis1. In addition, the prevalence of allergic sensitization is up to 50% in Sweden and in many other European countries 2,3. The total cost of allergic rhinitis in Sweden, with a population of 9.5 million (in 2014), has been estimated at \euro1.3 billion annually 4. Treating these patients with allergen immunotherapy (AIT) is cost-effective5. To date, AIT is the only treatment that affects the long-term development of allergic rhinoconjunctivitis. It induces clinical tolerance primarily by stimulating regulatory T (Treg) cells, attenuating T helper 2 (Th2) responses and inducing blocking antibodies6. Conventional AIT with subcutaneous injections is effective, but consumes time and resources 7,8. Therefore, despite its advantages in allergic rhinitis, AIT has not achieved its full potential. In Sweden, only 15/10,000 receive this treatment, and figures vary worldwide 9 .
AIT improves symptom, medication and combined symptom and medication scores (MS) in patients with allergic rhinoconjunctivitis10. A randomized placebo-controlled trial with subcutaneous immunotherapy (SCIT) with birch pollen allergen reduced the symptom score by 40% over placebo 11. In a review article of SCIT and sublingual immunotherapy (SLIT) trials, SCIT was reported to reduce nasal and ocular symptoms by 32–36% compared with placebo, whereas SLIT produced a reduction of 26–36% compared with placebo 12. In an open intralymphatic immunotherapy (ILIT) study, hay-fever patients received only three monthly allergen injections directly into the inguinal lymph nodes and an accumulated dose of only 3,000 standardized quantified units (SQ-U) in contrast to approximately 3,000,000 SQ-U with SCIT. Greater efficacy and safety, and faster relief of symptoms were observed after ILIT than after SCIT13. The study was followed by a few smaller studies of which five 14-18 confirmed the conclusion from the original trial, whereas one showed no benefit of ILIT19. Recently we performed a small open pilot study of 10 patients treated with ILIT for birch or grass pollen allergy. We concluded that ILIT was associated with improved quality of life, reduced symptoms, and beneficial immunological changes18. However, further studies are required to determine whether ILIT can induce clinical effects similar to those of SCIT concerning rhinitis symptoms and how ILIT affects immune responses20.
The objective was to evaluate whether ILIT can be an alternative to SCIT and SLIT. We also aimed to determine its safety, efficacy and immune modulatory effects, including changes in spontaneous and allergen-induced cytokine and chemokine production, and proportions of circulating T helper cell subsets.