Late responses affecting the skin are abrogated by repeated low-dose intradermal allergen

Publushed Online: September 11, 2012

High dose subcutaneous allergen immunotherapy (containing 5-20 mcg of major allergens), is clinically effective and associated with inhibition of allergen-induced late cutaneous (skin) responses  (Francis et al., The Journal of Allergy & Clinical Immunology (JACI) (2008) 121:1120-25). In contrast, the use of low dose subcutaneous allergen immunotherapy has been shown to be ineffective (Van Metre et al., The Journal of Allergy & Clinical Immunology (1980) 65:288-97). Uncontrolled reports dating from the early 20th century suggest that low dose intradermal allergen might be clinically effective.

Recently, in The Journal of Allergy & Clinical Immunology, Rotiroti et al. investigated the effect of repeated intradermal grass pollen on cutaneous reactivity to allergen. Thirty adults with dual sensitivity to grass and tree pollens were randomized to receive: 1) six repeat intradermal injections at two week intervals of grass pollen extract (each containing 7 ng Phl p 5), 2) two intradermal injections separated by 10 weeks, or 3) a single intradermal injection at 10 weeks (10 per group). At the end of the study, cutaneous early and late responses were measured following the double-blind intradermal injection of both grass and birch pollen extracts. Allergen-specific IgG levels and inhibitory function were also measured.

Participants who received six fortnightly intradermal grass pollen injections had markedly smaller cutaneous late responses to grass pollen than controls who received two injections separated by 10 weeks (p<0.01) or a single injection (p<0.001). During the 6 intradermal injections the cutaneous late response was almost completed inhibited (area reduced by over 90%) and was associated with induction of grass pollen-specific IgG antibodies with inhibitory function against IgE in an in vitro bioassay. Suppression was observed whether late responses were measured on arms or the back. Early responses were equivalent in all groups. No differences in intradermal responses to birch pollen were observed.

The authors’ findings suggest that repeated low dose intradermal grass pollen could mirror physiologic and immunologic changes seen with high dose subcutaneous immunotherapy. Whether the intradermal route using 1000-fold lower doses of allergen compared to the conventional subcutaneous route is also clinically effective and induces long term tolerance remains to be tested.


The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

AAAAI - American Academy of Allergy Asthma & Immunology