Intralymphatic immunotherapy improves grass pollen allergic rhinoconjunctivitis: A 3-year randomized placebo-controlled trial

J Allergy Clin Immunol. 2021 Mar;147(3):1011-1019. doi: 10.1016/j.jaci.2020.07.002. Epub 2020 Jul 15.


Background: Allergic rhinoconjunctivitis is a global health problem. Different allergen immunotherapy regimes are marketed but have low adherence because they are expensive, complex, and time-consuming. New allergen immunotherapy forms are needed.

Objective: In a 3-year follow-up double-blind randomized placebo-controlled trial, we aimed to investigate the effect of intralymphatic allergen immunotherapy (ILIT).

Methods: Patients with grass pollen rhinoconjunctivitis were treated with 3 ILIT injections and an ILIT booster 1 year later, 3 ILIT injections and a placebo booster, or 3 placebo injections and a placebo booster. Primary outcome was improvement in a combined symptom and medication score (cSMS). A novel evaluation tool with a linear regression model of cSMS and grass pollen counts was developed. Secondary outcomes were changes in grass specific immunoglobulins and skin and nasal provocation tests to grass pollen.

Results: A total of 36 patients were included. Log10-transformed cSMS was reduced by 0.30 (95% CI, 0.11-0.49; P = .002), equaling 48.5% (95% CI, 24.5%-62%), in the entire 3-year follow-up period, significant only in the first follow-up season but not in the second and third seasons. The regression model showed a 37% (P < .001) reduction in cSMS. The booster injection 1 year later had no additional effect. Secondary, repeated measures of IgE and IgG4 to grass showed significant between-group difference and within-group change in the ILIT groups. No change in provocation test results was found.

Conclusions: ILIT gives a substantial reduction in grass pollen allergy symptoms and use of rescue medication, significant in the first season after treatment. A booster injection had no additional effect.

Keywords: Allergic rhinoconjunctivitis; allergen immunotherapy; combined symptom medication score; intralymphatic immunotherapy; outcome parameters; ultrasound-guided injections.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology
  • Antigens, Plant / immunology
  • Conjunctivitis, Allergic / immunology
  • Conjunctivitis, Allergic / therapy*
  • Desensitization, Immunologic / methods*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Intralymphatic
  • Male
  • Placebo Effect
  • Poaceae / immunology
  • Pollen / immunology
  • Rhinitis, Allergic / immunology
  • Rhinitis, Allergic / therapy*
  • Severity of Illness Index
  • Treatment Outcome


  • Allergens
  • Antigens, Plant