Relief of Hay-Fever by Intradermal Injections of Pollen Extract

Phillips, E. W. J.

doi:10.1001/jama.1926.02670290022008

Cited by 48 publications

(34 citation statements)

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“…11 Second, the late-phase response induced by this dose corresponds to an average diameter of approximately 10 cm, a size that we considered to be at the limits of tolerability for patients for a routine treatment, especially as the response can be much larger in a proportion of subjects. Although it is impossible to equate this dosage precisely with that used in the uncontrolled historical studies of Phillips,12,13 it is notable that he described his treatment as inducing 'a local reaction about the size of the patient's palm', 12 which is similar to the response size we induced.…”

Section: Resultsmentioning

confidence: 81%

“…The concept of therapeutic intradermal allergen inoculation is not without precedent. In 1926, Phillips, a physician dworking in Arizona, published a preliminary account of his uncontrolled experiences with intradermal grass pollen immunotherapy in 29 patients, 12 extended to 322 patients by 1933, 13 > 90% of whom obtained 'satisfactory relief'. However, no randomised controlled trial (RCT) has previously addressed the efficacy of this approach.…”

Section: Discussionmentioning

confidence: 99%

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A randomised placebo-controlled trial investigating efficacy and mechanisms of low-dose intradermal allergen immunotherapy in treatment of seasonal allergic rhinitis

et al. 2016

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BackgroundWe previously reported that repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses, comparable with conventional high-dose subcutaneous and sublingual immunotherapy.ObjectiveTo evaluate the efficacy and mechanism of grass pollen intradermal immunotherapy for treatment of allergic rhinitis.DesignA Phase II, double-blind, randomised controlled parallel-group trial.SettingSingle-centre UK study.ParticipantsAdults aged 18–65 years, with grass pollen-induced allergic rhinoconjunctivitis.InterventionsSeven 2-weekly intradermal injections were given into the forearm, containing eitherPhleum pratensesoluble grass pollen extract (7 ng of the major allergen Phl p 5) or histamine control.Main outcome measuresThe primary outcome was a combined symptom and medication score (CSMS) during the 2013 grass pollen season. Secondary clinical outcomes were overall symptom scores; individual symptoms scores for nose, mouth, eyes and lungs; overall medication scores; CSMSs during the peak season; visual analogue scale (VAS) scores for nose and eye symptoms; Mini Rhinitis Quality of Life Questionnaire scores; health-related quality-of-life scores (European Quality of Life-5 Dimensions, 5-levels); a global evaluation of symptoms, number of symptom-free and medication-free days; number of days when prednisolone was used; and adverse events. Mechanistic studies included measurement of late-phase skin response sizes, allergen-specific antibody titres, analysis of skin biopsies and basophil activation tests.ResultsThere was no significant difference in CSMSs between treatment arms [difference in median area under curve (AUC) 14, 95% confidence interval (CI) –172.5 to 215.1;p = 0.80]. Paradoxically, among the secondary outcomes, nasal symptoms measured with daily scores were higher in the active arm (difference in median AUC 35, 95% CI 4.0 to 67.5;p = 0.03), with a trend for higher nasal symptoms measured by VASs (difference in median AUC 53, 95% CI –11.6 to 125.2;p = 0.05). No differences were seen in other clinical outcomes in the main intention-to-treat analysis. In mechanistic studies, active treatment increasedP. pratense-, Phl p 1- and Phl p 5-specific immunoglobulin E (allp = 0.001) compared with the control. T cells cultured from skin biopsies of active intradermal immunotherapy subjects showed higher T helper type 2 cell (Th2) marker CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) expression (p < 0.05) and lower T helper type 1 cell marker CXCR3 [chemokine (C-X-C Motif) receptor 3] expression (p < 0.05), respectively. Interleukin 5 messenger ribonucleic acid, measured by microarray, was more highly expressed by cultured skin T cells in the active arm (p < 0.05). Late-phase skin responses to grass pollen were still inhibited up to 7 months after intradermal immunotherapy (p = 0.03), but not at 10–13 months’ time points.LimitationsGrass pollen doses were not increased during the course, as our proof-of-concept trial showed that repeating the same doses was sufficient to achieve almost complete late-response suppression. Injections were not continued throughout the season, as previous subcutaneous grass pollen immunotherapy trials have demonstrated preseasonal regimen efficacy.ConclusionsIntradermal immunotherapy suppressed late-phase skin responses to allergen, but was not clinically effective. The intervention appeared to have an immunological priming effect and exacerbated certain seasonal symptoms, notably in the nose.Future workFurther studies on low-dose intradermal grass pollen immunotherapy are not recommended because of our demonstrated worsening of allergic rhinitis symptoms and immunological priming. The findings are of great significance for other novel immunotherapies targeting the skin, such as epicutaneous techniques.Trial registrationCurrent Controlled Trials ISRCTN78413121.FundingThis project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

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Section: Resultsmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

A randomised placebo-controlled trial investigating efficacy and mechanisms of low-dose intradermal allergen immunotherapy in treatment of seasonal allergic rhinitis

et al. 2016

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Vieira-Hernández¹,

Capriles‐Hulett²,

Sánchez‐Borges³

et al. 2018

RAM

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Antecedentes: La inmunoterapia subcutánea acuosa a altas dosis es una ruta validada y efectiva de administración de alérgenos para el ácaro del polvo doméstico y alergias al polen.Objetivos: Estudio de definición conceptual empleando inmunoterapia intradérmica (ITID) con alérgenos de ácaros (Dermatophagoides pteronyssinus/Dermatophagoides farinae [Dp/Df] y Blomia tropicalis [Bt]) a bajas dosis; se llevó a cabo en niños con rinitis alérgica sintomáticos a la exposición de polvo de casa. Métodos: A ocho pacientes sin uso previo de inmunoterapia, con pruebas de punción cutánea positivas e IgE sérica específica a una mezcla de Dp/Df y Bt, se les administraron por tres meses 0.05 mL de ITID semanalmente, provenientes de una preparación fenolizada albúmino-salina y contentiva de bajas dosis de ácaros (8.3 AU= 5 ng de Dp/Df y 2.5 DBU de Bt). Los síntomas nasales (Total Nasal Symptom Score) y los faciales (Escala Análoga Visual) fueron registrados dos semanas antes del tratamiento y en el transcurso una vez a la semana. Al comienzo y al final se realizaron pruebas cutáneas diluidas y seriadas (1/100-1/1.000.000) y determinaciones de IgG4 en el suero para los alérgenos. Resultados: Los valores de las escalas sugirieron mejoría clínica. Existió disminución significativa de los diámetros de las pápulas de las pruebas diluidas y seriadas, así como aumento de los valores de la IgG4 sérica al final del tratamiento. La ITID fue bien tolerada.Conclusión: Si estudios ulteriores confirman los presentes hallazgos, se podría promover una mayor utilización de la inmunoterapia alérgeno-específica.

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“…However, there are limited uncontrolled historical reports of true intradermal allergen immunotherapy that are necessarily limited to smaller doses than tolerated by the subcutaneous route because of prominence of local reactions. In 1926, Phillips, 10 working in Arizona, published a preliminary account of this treatment in 29 patients, 6 which was extended to 322 patients by 1933, 10 more than 90% of whom obtained ''satisfactory relief.'' To our knowledge, this phenomenon of intradermal injection with low-dose allergen extracts has not been readdressed since the work of Phillips.…”

Section: Discussionmentioning

confidence: 99%

Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses

Rotiroti

Shamji

Durham

et al. 2012

Journal of Allergy and Clinical Immunology

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Relief of Hay-Fever by Intradermal Injections of Pollen Extract

Cited by 48 publications

References 1 publication

A randomised placebo-controlled trial investigating efficacy and mechanisms of low-dose intradermal allergen immunotherapy in treatment of seasonal allergic rhinitis

A randomised placebo-controlled trial investigating efficacy and mechanisms of low-dose intradermal allergen immunotherapy in treatment of seasonal allergic rhinitis

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

Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses

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