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Cho, Lee, Park, Kwon, and Kim: Safety of ultrarush allergen subcutaneous immunotherapy in children with allergic disease

Abstract

Purpose

Ultrarush immunotherapy (ultra-RIT) is more convenient and higher compliant than conventional immunotherapy, but it has rarely used in clinical practice due to severe systemic reactions. This study aimed to determine the safety of ultra-RIT in children and adolescents.

Methods

We investigated 19 patients who received ultra-RIT with the same schedule between January 2011 and May 2016. They were sensitized to house dust mites (HDMs) and/or pollen and had their symptoms associated with positive allergens. Over a 1-day hospitalization period, all patients received ultra-RIT subcutaneously 3 times, increasing at hourly intervals. Systemic reactions were classified according to the World Allergy Organization grade system.

Results

Systemic reactions occurred in 14 patients (73.7%). The mean time to adverse reactions after the last injection was 36 minutes, and the majority of systemic reactions were pruritus and urticaria. In addition, the injection of HDM alone or HDM plus pollen caused more than grade 2 systemic reactions in about 50% each of the patients.

Conclusion

Since ultra-RIT caused a higher incidence of systemic reactions in children and adolescents, it should be carried out cautiously in the hospitalization rather than the office.

Figures and Tables

Fig. 1

Protocol for ultrarush immunotherapy. Novo-Helisen Depot (Allergopharma Joachim Ganzer KG, Reinbeck, Germany) with allergen concentration 5,000 units/mL was injected 3 times at 1-hour interval for 3 hours subcutaneously.10 Third injected dose was 50% maximal allergen dose. Maintenance treatment was started at 2 weeks after rapid induction. Antihistamine was taken 1 week prior to immunotherapy and two more weeks before the next visit. BP, blood pressure; HR, heart rate; RR, respiratory rate.

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Table 1

Demographic characteristics in patients with ultrarush subcutaneous immunotherapy

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Characteristic Total (n=19) Ultrarush IT cases P-value
Continuation (n=14) Dropout* (n=5)
Age (yr) 12.1 ± 3.9 10.7 ± 2.2 15.8 ± 5.4 0.103
Male sex 13 (68.4) 10 (71.4) 3 (60) 0.637
Eosinophil count (/µL) 305.3 ± 336.6 230.0 ± 300.3 516.0 ± 375.9 0.176
Total IgE (IU/mL) 522.8 ± 968.0 258.3 ± 235.9 1,263.2 ± 1,762.1 0.272
Allergen 0.203
 House dust mite 11 (57.9) 9 (64.3) 2 (40.0)
 House dust mite with pollen§ 7 (36.8) 5 (35.7) 2 (40.0)
 Pollen§ 1 (5.3) 0 (0) 1 (20.0)
Disease 0.356
 Asthma only 1 (5.3) 1 (7.1) 0 (0)
 AR only 8 (42.1) 4 (28.6) 4 (80.0)
 AR & asthma 6 (31.6) 5 (35.7) 1 (20.0)
 AR & AD 2 (10.5) 2 (14.3) 0 (0)
 AR & AC 2 (10.5) 2 (14.3) 0 (0)

Values are presented as mean±standard deviation or number (%).

IT, immunotherapy; AR, allergic rhinitis; AD, atopic dermatitis; AC, allergic conjunctivitis.

*Those who gave up immunotherapy were classified among the 19 patients who underwent ultrarush allergen immunotherapy. There was no statistical significance comparing the continuation and dropout groups with Student t-test. There was no statistical significance in the both groups, tested by chi-square test. §Pollen includes tree pollen (alder, hazel, and birch), grass (rye and timothy), and weeds (mugwort and ragweed).

Table 2

Systemic reactions grade of ultrarush subcutaneous immunotherapy

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WAO SR grade* No. of patients (%) Mean onset time of SR (min) No. of epinephrine IM (%)
Grade 1 6 (42.9) 140.3 2 (33.3)
 Urticaria 3 287.7 1
 Angioedema 1 165 1
 Cough 1 143 0
 Eye Itching 1 270 0
Grade 2 5 (35.7) 154.5 2 (33.3)
 Urticaria and dyspnea 2 232.5 0
 Urticaria and wheezing 3 131.3 2
Grade 3 3 (21.4) 142.1 2 (33.3)
 Angioedema and dyspnea with urticaria 1 245 0
 Urticaria and wheezing 2 195 2
Grade 4 0 - -
Grade 5 0 - -
Total 14 (100) 154.5 (range, 70–403) 6 (42.9)

WAO SR, World Allergy Organization systemic reaction; IM, intramuscular.

*In 2010, the WAO systemic adverse events in subcutaneous immunotherapy was as follows: Grade 1 was defined as the presence of sign and/or symptom of 1 organ, such as skin, upper respiratory tract, conjunctival symptoms and so on. Grade 2 was defined as the presence of signs or symptoms involving one or more organs, such as lower respiratory, gastrointestinal, or uterine cramps. Grade 3 was a lower respiratory condition with no response to inhaled bronchodilator therapy. Grade 4 was classified as respiratory symptoms due to respiratory failure or cardiovascular symptoms, and grade 5 as death.1 Epinephrine treatment was performed in cases involving more than 2 organs with dyspnea, and also in failure of first treatment. There was no response to inhalation therapy for dyspnea.

Table 3

Side effects during ultrarush subcutaneous immunotherapy according to allergen and allergic disease

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Variable Total number No. of SR (%) SR ≥ grade 2*, n (%) P-value
Allergen 0.710
 HDM 11 9 (81.8) 5 (45.6) 0.637
 HDM with pollen 7 4 (57.1) 2 (50.0)
Disease 0.625
 Asthma only 1 1 (7.1) 0 (0) 0.668
 AR only 8 6 (42.9) 4 (50.0)
 AR & asthma 6 4 (28.6) 3 (37.5)
 AR & AD 2 2 (14.3) 0 (0)
 AR & AC 2 1 (7.1) 1 (12.5)

SR, systemic reaction; HDM, house dust mites; AR, Allergic Rhinitis; AC, allergic conjunctivitis; AD, atopic dermatitis.

*Grade 2 or more was accompanied by dyspnea or low respiratory symptoms. According to allergen or allergic disease all systemic reactions were analyzed using the chi-square statistical method. According to allergen or allergic disease grade 2 or more systemic reactions were analyzed using the chi-square statistical method.

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Ja Kyoung Kim
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