Low-Dose Subcutaneous Immunotherapy for Dust Mite in Pediatric Allergic RhinitisYehonatan Pasternak1,2,3, Shirley Sarig Epstein2,3, Eris Greenbaum1, Yoram Faitelson1,2, Nufar Marcus1,2, Nirit Segal1,2, Basel Badarneh1,2, Siril Yoffe1,2, Liad Avneri1,2, Avraham Beigelman1,21 Schneider Children’s Medical Center in Israel, Kipper Institute of Allergy and Immunology, Petah Tikva, Israel. 2 Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel.3 Pediatrics A, Schneider Children’s Medical Center in Israel, Petah Tikva, Israel.Word count: 1031Abbreviations: AR – allergic rhinitis, SCIT – subcutaneous immunotherapy, HDM – house dust mite, AU – allergy units, TNSS – Total Nasal Symptom Score, TMS – Total Medication Score,Conflicts of interests: The authors declare that they have no conflicts of interest related to this study.To the Editor:Pediatric allergic rhinitis (AR) significantly impacts the quality of life of affected children. Allergen immunotherapy is an effective therapy that alleviates symptoms, and more importantly\RL, changes the natural history of this disease1. Subcutaneous allergen immunotherapy (SCIT) is the most widespread method of allergen immunotherapy in pediatric patients with AR\RL2. One of the most common causative allergens worldwide is house dust mite (HDM)3. Clinical guidelines suggest that an effective SCIT protocol for HDM should aim for a maintenance dose of 500–2000 allergy units (AU) that includes both major species: D farinae and D pteronyssinus 4. Previous studies have shown variability in dosing protocols among caregivers and highlighted the need for more consensus on treatment parameters like dose and duration in HDM SCIT5. Moreover, most of the data on allergen immunotherapy originated from studies conducted among adults, and there is a paucity of data on effective HDM SCIT dosing regimens in the pediatric population. Several reports called for trials with efficacy criteria tailored to HDM-induced allergic disease, but these recommendations were not strongly pursued6,7.In our allergy clinic we observed a substantial incidence of systemic allergic reactions to SCIT in the mid-high doses. This prompted us to recently transition from administering a maintenance dose of 500 AU of HDM extract to a lower dose of 50 AU. Our data show that 95.6% of systemic reactions occurred at doses in the range of 100–500 AU. This supports the rationale for adopting a lower maintenance dose8. However, patients who report significant nasal symptoms with the low-dose SCIT are gradually increased to standard-dose maintenance. As a result, our patients can be classified into two groups: those who stayed on the low-dose regimen and those who required an increase to the standard maintenance dose due to persistent symptoms. . Patients who also received SCIT for other aeroallergens (e.g., pollens) were treated using standard dosing protocols.In a cross-sectional comparative study, we aimed to evaluate the disease burden of AR among children treated at our institute between May 2018 and January 2024. We compared between those who received a lower dose of dust mite SCIT (50 AU) and those who received the traditional SCIT dose of 500 AU. We estimated the disease burden of AR and medication use over the two weeks preceding the survey, in patients who had been on a SCIT maintenance dose for over six months. Specifically, we assessed the Total Nasal Symptom Score (TNSS) and the Total Medication Score (TMS)9 in these patients.The TNSS evaluates the severity of symptoms across four categories: sneezing, rhinorrhea, nasal itching, and nasal obstruction. Each category is rated on a scale from 0 (no symptoms) to 3 (severe symptoms that are hard to tolerate and that disrupt daily activities). The overall TNSS is the sum of the scores from these four categories, with a maximum possible score of 12.9 The TMS considers only the most potent medication used during the previous 14 days, rated on a scale from 0 to 3 (0 = no treatment, 1 = oral H1 antihistamine, 2 = intranasal corticosteroid, 3 = oral corticosteroid)9. In the statistical analysis, means ± standard deviations were calculated for continuous variables, and counts (%) for categorical data. Data were compared between groups using one-way ANOVA for continuous variables, and Fisher’s Exact test for categorical data. Ethical approval for this study was obtained from the local ethics committee. Written informed consent was obtained from the parents or legal guardians of all enrolled children.We analyzed data collected from 71 pediatric patients who started HDM SCIT before age 18 years. All the patients had characteristic symptoms of AR, with a positive (>3mm) skin test or positive (>0.35 KU) specific immunoglobulin E for dust mite (+/- pollens). The mean age was 17.3 years.Of the 71 patients, 46 (65%) started on a low-dose protocol. Eventually, 32 (70%) continued to receive low-dose maintenance (50 AU) and 14 (30%) switched to standard-dose maintenance due to ongoing symptoms. Classifying the patients according to their final maintenance treatment dosage yielded 32 in the low-dose group, and 39 who initially or eventually received the standard dose of 500 AU. No significant differences were found between the groups in terms of age, gender, history of asthma, or pollen allergy.The low-dose SCIT group demonstrated a TNSS of 5.59 (±2.47), similar to the standard-dose group (5.35±2.91, p=0.72). TMS was also comparable between the groups (1.68 vs. 1.23, p=0.54) (Table 1).Our findings suggest that the disease burden of AR may be similar for children treated with low-dose (50 AU) HDM SCIT and those treated with standard-dose SCIT (500 AU). The lower dose approach has the potential benefit of reducing SCIT-related side effects. However, 30% of the patients had to switch to higher-dose SCIT due to persistent AR symptoms. Therefore, a conservative approach—starting with low-dose SCIT, monitoring for ongoing symptoms, and increasing the dose only in patients with significant residual symptoms—may help minimize SCIT-related side effects.The cross-sectional nature of our study precluded assessing treatment efficacy through changes in the TNSS score from baseline. Additionally, most of the patients received SCIT for other aeroallergens (e.g., pollens) concomitant with HDM. However, as HDM is the major allergen responsible for SCIT-related systemic reactions at our institution8, establishing HDM SCIT protocols that would reduce the incidence of these systemic allergic reactions would be highly desirable. Finally, our sample size was relatively small, raising the possibility that we lacked sufficient statistical power to detect differences between groups. Given these limitations, this study should be viewed as hypothesis-generating, laying the scientific foundation for a larger, prospective investigation into HDM SCIT dosing protocols.In conclusion, our findings suggested that low-dose (50 AU) SCIT for pediatric allergic rhinitis may offer comparable symptom control and medication use to the standard-dose regimen, while potentially reducing systemic allergic reactions. As some patients still required SCIT dose escalation, a stepwise approach may help minimize adverse effects while maintaining treatment efficacy.Keywords : allergic rhinitis, house dust mite, subcutaneous immunotherapy, dosing, pediatricDr. Yehonatan Pasternak Schneider Children’s Medical Center in Israel Kipper Institute of Allergy and Immunology, Petah Tikva, IsraelTable 1. Characteristics and Disease Burden Scores of Low-Dose (50 AU) versus Standard-Dose (500 AU) Subcutaneous Allergen Immunotherapy.