Intradermal grass pollen immunotherapy increases T H 2 and IgE responses and worsens respiratory allergic symptoms

Abstract

BackgroundRepeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy.ObjectiveWe sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis.MethodsWe randomly assigned 93 adults with grass pollen–induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment.ResultsThere was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, −172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, −11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense–specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03).ConclusionIntradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms.

Intradermal immunotherapy with low-dose house dust mite allergens in patients with allergic rhinitis: A proof-of-concept study

“…Each 0.05 mL volume from this newly prepared fl ask was used for the IDIT injections containing approximately 8.3 AU of Dp/Df or 0.05 micrograms (5 ng) of HDM major allergens. This 5 ng concentration of HDM allergens is quite like the nanograms concentrations employed in previous reports for grass pollen IDIT; 22,25 for the Blomia tropicalis allergens a 2.5 DBU/0.05 mL was correspondingly estimated. This 30 mL multiple-injection fl ask allowed for ease of operation in our weekly busy clinic; it was properly stored at 4-8 °C and taken out of the refrigerator once a week.…”

“…Our patients received only 5 ng (0.05 micrograms) of HDM major allergens/0.05 mL injection/week, all throughout the 12-week study period (a cumulative dose of 0.6 micrograms/12 weeks). Previous grass allergens IDIT studies that employed a 7 ng dose 22,25 served as an orientation for our HDM concentration choice; no such information exists for Blomia tropicalis, but we followed the same dilution criteria for HDM injections: each 0.05 mL IDIT weekly injections contained 2.5 DBU of the Blomia tropicalis allergens. On the other hand, the volume of weekly injections employed was reduced 10 times (0.05 mL IDIT vs 0.5 mL SCIT) and employing the 0.3.mL/31 G needle syringes allowed for a fi ne tuning when performing the "peau d'orange" technique bleb.…”

“…There are very few studies employing the IDIT technique 19,20,21,22,23,24,25 and none, known to us, with HDM allergens. Doses employed in previous reports of IDIT with grass pollen were guided by the suppression of late cutaneous reactions, 22,25 with cu- mulative doses reaching 1000 fold less allergen vs conventional SCIT over a year´s time (nanograms vs micrograms); furthermore, in these studies, injections were given every two weeks for three months and spaced out afterwards.…”

“…23,24 However, later fi ndings from a grass pollen allergy intradermal immunotherapy (IDIT) study have raised signifi cant controversies around it´s effi cacy. 25 A recent book chapter on AIT by Nelson 12 makes no mention of this route of administration and to our knowledge there are no reports of IDIT use with the HDM.…”

EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis

“…inflammation in the skin. 126 The intralymphatic route, using a grass pollen extract and a modified cat allergen extract, showed efficacy in some trials 127,128 but not in others. 129 …”